Skip to main content

Squamous differentiation and retinoids

  • Chapter
Head and Neck Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 74))

Abstract

Retinoids are structural or functional analogues of vitamin A, or retinol. They exert profound effects on the growth, maturation, and differentiation of many cells types, particularly epithelial cells, both in vivo and in vitro [18]. Vitamin A exerts a major effect on normal differentiation of epithelial cells, including those lining the oral cavity and upper aerodigestive tract [9]. The maintenance of the mucus-secreting function of these cells depends on the continuous presence of vitamin A. In its absence, squamous metaplasia develops that can be reversed by vitamin A replenishment [814]. ß-alltrans-retinoic acid (tRA) can replace vitamin A in restoration of normal differentiation of epithelial tissues in vitamin A-deficient animals [1419]. It is thought that squamous metaplasia in the upper aerodigestive epithelium is a precursor of certain cancers [20] and that agents like retinoids, which suppress keratinization and restore the normal nonkeratinizing phenotype to premalignant and malignant lesions, may also restore their responsiveness to normal growth control mechanisms. Consequently, such agents could suppress carcinogenesis and be useful in the prevention and treatment of squamous cell carcinomas [2123]. This chapter describes the effects of retinoids on squamous differentiation in normal, premalignant, and malignant epithelial tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lotan R. Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 605:33–91, 1980.

    PubMed  CAS  Google Scholar 

  2. Roberts AB, Sporn MB. Cellular biology and biochemistry of the retinoids. In: MB Sporn, AB Roberts, DS Goodman, eds. The Retinoids. Orlando: Academic Press, pp 209–286, 1986.

    Google Scholar 

  3. Sherman MI (ed), Retinoids and Cell Differentiation. Boca Raton, FL: CRC Press.

    Google Scholar 

  4. Gudas LJ. Molecular mechanisms of retinoid action. Am J Respir Cell Mol Biol 2:319–320, 1989.

    Google Scholar 

  5. Jetten AM. Multistep process of squamous differentiation in tracheobronchial epithelial cells in vitro: Analogy with epidermal differentiation. Environ Health Perspect 80: 149–160, 1989.

    PubMed  CAS  Google Scholar 

  6. Jetten AM. Multi-stage program of differentiation in human epidermal keratinocytes: Regulation by retinoids. J Invest Dermatol 95:44–46, 1990.

    Google Scholar 

  7. Amos B, Lotan R. Retinoid-sensitive cells and cell lines. Methods Enzymol 190:217–225, 1991.

    Google Scholar 

  8. DeLuca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 5:2924–2933, 1991.

    CAS  Google Scholar 

  9. Wolbach SB, Howe PR. Tissue changes following deprivation of fat soluble vitamin A. J Exp Med 42:753–777, 1925.

    PubMed  CAS  Google Scholar 

  10. Wolbach SB. Effects of vitamin A deficiency and hypervitaminosis in animals. In: WH Sebrell, RS Harris, eds. The Vitamins, vol 1. New York: Academic Press, 1956, pp 106–137.

    Google Scholar 

  11. Wong YC, Buck RC. An electron microscopic study of metaplasia of the rat tracheal epithelium in vitamin A-deficiency. Lab Invest 24:55–66, 1971.

    PubMed  CAS  Google Scholar 

  12. Harris CC, Silverman T, Smith JM, Jackson F, Boren HG. Proliferation of tracheal epithelial cells in normal and vitamin A-deficient Syrian golden hamsters. J Natl Cancer Inst 51:1059–1062, 1973.

    PubMed  CAS  Google Scholar 

  13. Chopra DP. Squamous metaplasia in organ culture of vitamin A-deficient hamster trachea. Cytokinetic and ultrastructural alterations. J Natl Cancer Inst 69:895–905, 1982.

    PubMed  CAS  Google Scholar 

  14. Chopra DP. Retinoid reversal of squamous metaplasia in organ cultures of tracheas derived from hamsters fed an vitamin A-deficient diet. Eur J Cancer Clin Oncol 9: 847–857, 1983.

    Google Scholar 

  15. Dowling JE, Wald G. The role of vitamin A acid. Vitam Horm 18:515–541, 1960.

    PubMed  CAS  Google Scholar 

  16. Sporn MB, Clamon GH, Dunlop NM, Newton DL, Smith JM, Saffiotti U. Activity of vitamin A analogues in cell cultures of mouse epidermis and organ cultures of hamster trachea. Nature 253:47–50, 1975.

    PubMed  CAS  Google Scholar 

  17. Sporn MB, Dunlop NM, Newton DL, Henderson WR. Relationships between structure and activity of retinoids. Nature 263:110–113, 1976.

    PubMed  CAS  Google Scholar 

  18. Chytil F. Retinolc acid: Biochemistry and metabolism. J Am Acad Dermatol 15:741–747, 1986.

    PubMed  CAS  Google Scholar 

  19. Darmon M. Retinoic acid in skin and epithelia. Semin Dev Biol 2:219–228, 1991.

    Google Scholar 

  20. Auerbach O, Stout AP, Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med 265:253–267, 1961.

    PubMed  CAS  Google Scholar 

  21. Saffioti U, Montesano R, Sellakumar AR, Bork SA. Experimental cancer of the lung. Inhibition by vitamin A of the induction of tracheobronchial metaplasia and squamous cell tumor. Cancer 20:857–864, 1967.

    Google Scholar 

  22. Sporn MB, Newton DL. Chemoprevention of cancer with retinoids. Fed Proc 38:2528–2534, 1979.

    PubMed  CAS  Google Scholar 

  23. Lotan R, Lippman SM, Hong WK. Retinoid modulation of squamous cell differentiation and carcinogenesis. Cancer Bull 43:490–498, 1991.

    Google Scholar 

  24. Eckert RL. Structure, function, and differentiation of the keratinocyte. Physiol Rev 69:1316–1346, 1989.

    PubMed  CAS  Google Scholar 

  25. Fuchs E. Epidermal differentiation: The bare essentials. J Cell Biol 111:2807–2814, 1990.

    PubMed  CAS  Google Scholar 

  26. Hohl D. Cornified cell envelope. Dermatologica 180:201–211, 1990.

    PubMed  CAS  Google Scholar 

  27. Darmon M, Rocher M, Cavey MT, Martin B, Ribald T, Delescluse C, Shroot B. Biological activity of retinoids correlates with affinity for nuclear receptors but not for cytosolic binding protein. Skin Pharm 1:161–175, 1988.

    CAS  Google Scholar 

  28. Ohayoun J-P, Gosselin F, Forest N, Winter S, Franke WW. Cytokeratin patterns of human oral epithelia: Differences in cytokeratin synthesis in gingival epithelium and the adjacent alveolar mucosa. Differentiation 30:123–129, 1985.

    Google Scholar 

  29. Thacher SM, Rice RH. Keratinocyte-specific transglutaminase of cultured human epidermal cells: Relation to cross-linked envelope formation and terminal differentiation. Cell 40:685–695, 1985.

    PubMed  CAS  Google Scholar 

  30. Thacher SM. Purification of keratinocyte transglutaminase and its expression during squamous differentiation. J Invest Dermatol 89:578–584, 1989.

    Google Scholar 

  31. Folk JE. Mechanisms and basis for specificity of transglutaminase-catalyzed ε-(γ-glutamyl) lysine bond formation. Adv Enzymol 54:1–54, 1983.

    PubMed  CAS  Google Scholar 

  32. Chakravarty R, Rice RH. Acylation of keratinocyte transglutaminase by palmitic and myristic acids in the membrane anchorage region. J Biol Chem 264:625–629, 1989.

    PubMed  CAS  Google Scholar 

  33. Rice RH, Green H. Relationship of protein synthesis and transglutaminase activity to formation of the cross-linked envelope during terminal differentiation of the cultured human epidermal keratinocyte. J Cell Biol 76:705–711, 1978.

    PubMed  CAS  Google Scholar 

  34. Simon M, Green H. Enzymatic crosslinking of involucrin and other proteins by keratinocyte particulates in vitro. Cell 40:677–683, 1985.

    PubMed  CAS  Google Scholar 

  35. Lichti U, Ben T, Yuspa SH. Retinoic acid-induced transglutaminase in mouse epidermal cells is distinct from epidermal transglutaminase. J Biol Chem 260:1422–1426, 1985.

    PubMed  CAS  Google Scholar 

  36. Rice RH, Thacher SM. In: J Breiter-Hahn, AG Matoltsky, KS Richards, eds. Biology of the Integument, vol 2. Heidelberg: Springer-Verlag, 1986, pp 752–761.

    Google Scholar 

  37. Hohl D, Mehrel T, Lichti U, Turnerm ML, Roop D, Steinert PM. Characterization of human loricrin structure and function of a new class of epidermal cell envelope proteins. J Biol Chem 266:6626–6636, 1991.

    PubMed  CAS  Google Scholar 

  38. Magnaldo T, Bernerd F, Asselineau D, Darmon M. Expression of loricrin is negatively controlled by retinoic acid in human epidermis reconstructed in vitro. Differentiation 49:39–46, 1982.

    Google Scholar 

  39. Marvin KW, George MD, Fujimoto W, Saunders N, Bernacki SH, Jetten AM. Cornifin: A new cross-linked envelope precursor in keratinocytes. Down regulation by retinoids. Proc Natl Acad Sci USA, 89:11026–11030, 1992.

    PubMed  CAS  Google Scholar 

  40. Simon M, Green H. Participation of membrane-associated proteins in the cross-linked envelope of the keratinocyte. Cell 36:827–834, 1984.

    PubMed  CAS  Google Scholar 

  41. Rice RH, Green H. The cornified envelope of terminally differentiated human epidermal keratinocytes consists of cross-linked protein. Cell 11:417–422, 1977.

    PubMed  CAS  Google Scholar 

  42. Rice RH, Green H. Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: Activation of cross-linking by calcium ions. Cell 18:681–694, 1979.

    PubMed  CAS  Google Scholar 

  43. Eckert RL, Green H. Structure and evolution of the human involucrin gene. Cell 46:583–589, 1986.

    PubMed  CAS  Google Scholar 

  44. Simon M, Green H. The glutamine residues reactive in transglutaminase-catalyzed cross-linking of involucrin. J Biol Chem 263:18093–18098, 1988.

    PubMed  CAS  Google Scholar 

  45. Green H, Watt FM. Regulation by vitamin A of envelope cross-linking in cultured keratinocytes derived from different human epithelia. Mol Cell Biol 2:1115–1117, 1982.

    PubMed  CAS  Google Scholar 

  46. Murphy GM, Flynn TC, Rice RH, Pinkus GS. Involucrin expression in normal and neoplastic human skin: A marker for keratinocyte differentiation. J Invest Dermatol 82:453–457, 1984.

    PubMed  CAS  Google Scholar 

  47. Banks-Schlegl S, Green H. Involucrin synthesis and tissue assembly by keratinocytes in natural and cultured human epithelia. J Cell Biol 90:732–737, 1981.

    Google Scholar 

  48. Klein-Szanto AJP, Boysen M, Reith A. Keratin and involucrin in preneoplastic and neoplastic lesions. Arch Pathol Lab Med 111:1057–1061, 1987.

    PubMed  CAS  Google Scholar 

  49. Zettergren JG, Peterson LL, Wuepper KD. Keratolinin: The soluble substrate of epidermal transglutaminase from human and bovine tissue. Proc Natl Acad Sci USA 81:238–242, 1984.

    PubMed  CAS  Google Scholar 

  50. Lobitz CJ, Buxman MM. Characterization and localization of bovine epidermal transglutaminase substrate. J Invest Dermatol 78:150–154, 1982.

    PubMed  CAS  Google Scholar 

  51. Passavant CW, Coulter SN, Wuepper KD. The identification of cDNA clones coding for a protein which reacts with anti-keratolinin. J Invest Dermatol 92:497, 1989.

    Google Scholar 

  52. Moore KG, Sartorelli AC. Annexin I and involucrin are cross-linked by particulate transglutaminase into the cornified cell envelope of squamous cell carcinoma Y1. Exp Cell Res 200:186–195, 1992.

    PubMed  CAS  Google Scholar 

  53. Ando Y, Imamura S, Owada MK, Kannagi R. Calcium-induced intracellular cross-linking of lipocortin I by tissue transglutaminase in A431 cells. J Biol Chem 266:1101–1108, 1991.

    PubMed  CAS  Google Scholar 

  54. Kvedar JC, Manabe M, Phillips SB, Ross BS, Baden HP. Characterization of sciellin, a precursor to the cornified envelope of human keratinocytes. Differentiation 49:195–204, 1992.

    PubMed  CAS  Google Scholar 

  55. Roop DR, Huitfeldt H, Kilkenny A, Yuspa SH. Regulated expression of differentiation-associated keratins in cultured epidermal cells detected by monospecific antibodies derived from different human epithelia. Differentiation 35:143–150, 1987.

    PubMed  CAS  Google Scholar 

  56. Fuchs E, Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell 19:1033–1042, 1980.

    PubMed  CAS  Google Scholar 

  57. Sun TT, Tseng SCG, Huang AJ-W, Cooper D, Schermer A, Lynch MH, Weiss R, Eichner R. Monoclonal antibody studies of mammalian epithelial keratins: A review. Ann NY Acad Sci 455:307–329, 1985.

    PubMed  CAS  Google Scholar 

  58. Franke WW, Schiller DL, Moll R, Winter S, Schmidt E, Engelbrecht I, Denk H, Krepier R, Platzer B. Diversity of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 153:933–959, 1981.

    PubMed  CAS  Google Scholar 

  59. Moll R, Franke WW, Schiller DL, Geiger B, Krepier R. The catalog of human cyto-keratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24, 1982.

    PubMed  CAS  Google Scholar 

  60. Moll R, Krepier R, Franke WW. Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23:256–269, 1983.

    PubMed  CAS  Google Scholar 

  61. Roop DR, Krieg TM, Mehrel T, Chung CK, Yuspa SH. Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis. Cancer Res 48:3245–3252, 1988.

    PubMed  CAS  Google Scholar 

  62. Nagle RB, Moll R, Weidauer H, Nemetschek H, Franke WW. Different patterns of cytokeratin expression in the normal epithelia of the upper respiratory tract. Differentiation 30:130–140, 1985.

    PubMed  CAS  Google Scholar 

  63. Fleckman P, Dale BA, Holbrook KA. Profilaggrin, a high molecular weight precursor of filaggrin in human epidermis and cultured keratinocytes. J Invest Dermatol 85:507–512, 1985.

    PubMed  CAS  Google Scholar 

  64. Asselineau D, Bernard BA, Bailly C, Darmon M. Retinole acid improves epidermal morphogenesis. Dev Biol 133:322–335, 1989.

    PubMed  CAS  Google Scholar 

  65. Rothnagel JA, Steinert PM. The structure of the gene for mouse filaggrin and a comparison of the repeating units. J Biol Chem 265:1862–1865, 1990.

    PubMed  CAS  Google Scholar 

  66. Manabe M, Sanchez M, Sun T-T, Dale BA. Interaction of filaggrin with keratin filaments during advanced stages of normal human epidermal differentiation and in ichtiosis vulgaris. Differentiation 48:43–50, 1991.

    PubMed  CAS  Google Scholar 

  67. Korge B, Gan S-O, Yoneda K, Compton JG, Volz A, Steinert PM, Ziegler A, Mischke D. Physical mapping of the epidermal differentiation markers loricrin, profilaggrin, and involucrin on chromosome lq21 by pulsed field electrophoresis. Clin Res 40:490A, 1992.

    Google Scholar 

  68. Lotan R, Pieniazek J, George MD, Jetten AM. Identification of a new squamous cell differentiation marker and its suppression by retinoids. J Cell Physiol 151:94–102, 1992.

    PubMed  CAS  Google Scholar 

  69. Jetten AM, Bernacki SH, Floyd EE, Saunders NA, Pieniazek J, Lotan R. Expression of a preprorelaxin-like gene during squamous differentiation of rabbit tracheobronchial epithelial cells and its suppression by retinoic acid. Cell Growth Differ 3:549–556, 1992.

    PubMed  CAS  Google Scholar 

  70. Rearick JI, Jetten AM. Accumulation of cholesterol 3-sulfate during in vitro squamous differentiation of rabbit tracheal epithelial cells and its regulation by retinoids. J Biol Chem 261:13898–13904, 1986.

    PubMed  CAS  Google Scholar 

  71. Rearick JI, Albro PW, Jetten AM. Increase in cholesterol sulfotransferase activity during in vitro squamous differentiation of rabbit tracheal epithelial cells and its inhibition by retinoic acid. J Biol Chem 262:13069–13074, 1987.

    PubMed  CAS  Google Scholar 

  72. Rearick JI, Hesterberg TW, Jetten AM. Human bronchial epithelial cells synthesize cholesterol sulfate during squamous differentiation in vitro. J Cell Physiol 133:573–578, 1987.

    PubMed  CAS  Google Scholar 

  73. Jetten AM, George MA, Nervi C, Boone LR, Rearick JI. Increased cholesterol sulfate and cholesterol sulfotransferase activity in relation to multistep process of differentiation in human epidermal keratinocytes. J Invest Dermatol 92:203–209, 1989.

    PubMed  CAS  Google Scholar 

  74. Jetten AM, George MA, Pettit GR, Rearick JI. Effects of bryostatins and retinoic acid on phorbol ester-and diacylglycerol-induced squamous differentiation in human tracheobronchial epithelial cells. Cancer Res 49:3990–3995, 1989.

    PubMed  CAS  Google Scholar 

  75. Jetten AM, Kim JS, Sacks PG, Rearick JI, Lotan D, Hong WK, Lotan R. Suppression of growth and squamous cell differentiation markers in cultured human head and neck squamous carcinoma cells by ß-all trans retinoic acid. Int J Cancer 45:195–202, 1990.

    PubMed  CAS  Google Scholar 

  76. Brod J, Bavelier E, Justine P, Weerheim A, Ponec M. Acylceramides and lanosterol-lipid markers of terminal differentiation in cultured human keratinocytes: Modulating effects of retinoic acid. In Vitro 27:163–168, 1991.

    Google Scholar 

  77. Lasnitzki I. Hypovitaminosis A in the mouse prostate gland cultured in chemically defined medium. Exp Cell Res 28:40–51, 1962.

    CAS  Google Scholar 

  78. Keenan KP, Combs JW, McDowell EM. Regeneration of hamster tracheal epithelium after mechanical injury. IV. Histochemical, immunocytochemical studies. Virchows Arch Cell Pathol 41:213–240, 1983.

    Google Scholar 

  79. Marchok AC, Cone V, Nettesheim P. Induction of squamous metaplasia (vitamin A deficiency) and hypersecretory activity in tracheal organ culture. Lab Invest 33:451–460, 1975.

    PubMed  CAS  Google Scholar 

  80. McDowell EM, Keenan KP, Huang M. Effects of vitamin A deprivation on hamster tracheal epithelium. A quantitative morphologic study. Virchows Arch [Cell Pathol] 45:197–219, 1984.

    CAS  Google Scholar 

  81. Harris CC, Sporn MB, Kaufman DG, Smith JM, Jackson FE, Saffiotti U. Histogenesis of squamous metaplasia in the hamster tracheal epithelium caused by vitamin A deficiency or benzo[a]pyrene ferric oxide. J Natl Cancer Inst 48:743–761, 1973.

    Google Scholar 

  82. Shin DM, Gimenez IB, Lee JS, Nishioka K, Wargovich MJ, Thacher S, Lotan R, Slaga TJ, Hong WK. Expression of epidermal growth factor receptor, polyamine levels, ornithine decarboxylase activity, micronuclei, and transglutaminase I in DMBA-induced hamster buccal pouch carcinogenesis model. Cancer Res 50:2505–2510, 1990.

    PubMed  CAS  Google Scholar 

  83. Gimenez IB, Shin DM, Bianchi AB, Roop DR, Hong WK, Conti CJ, Slaga TJ. Changes in keratin expression during 7,12-dimethylbenz[a]anthracene-induced hamster cheek pouch carcinogenesis. Cancer Res 50:4441–4445, 1990.

    Google Scholar 

  84. Ford JR, Howe-Terzaghi M. Basal cells are the progenitors of primary tracheal epithelial cell cultures. Exp Cell Res 198:69–77, 1992.

    PubMed  CAS  Google Scholar 

  85. Sigler RE, Newkirk C, McDowell EM. Histogenesis and morphogenesis in epidermoid metaplasia in hamster tracheal organ explant culture. Virchows Arch [B] 55:47–55, 1988.

    CAS  Google Scholar 

  86. Jetten AM, George MA, Smits HL, Vollberg TM. Keratin 13 expression is linked to squamous differentiation in rabbit tracheal epithelial cells and down-regulated by retinoic acid. Exp Cell Res 182:622–634, 1989.

    PubMed  CAS  Google Scholar 

  87. Shafer WG, Hine MA, Levy BM. A Textbook of Oral Pathology. Philadelphia: WB Saunders, 1974, pp 81–211.

    Google Scholar 

  88. Cline PR, Rice RH. Modulation of involucrin and envelope competence in human keratinocytes by hydrocortisone, retinyl acetate, and growth arrest. Cancer Res 43:3203–3207, 1983.

    PubMed  CAS  Google Scholar 

  89. Reiss M, Pitman SW, Sartorelli AC. Modulation of the terminal differentiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid. J Natl Cancer Inst 74:1015–1023, 1985.

    PubMed  CAS  Google Scholar 

  90. Sundqvist K, Liu Y, Arvidson K, Ormstad K, Nilsson L, Toftgard R, Grafstrom RC. Growth regulation of serum-free cultures of epithelial cells from normal human buccal mucosa. In Vitro Cell Dev Biol 27:562–568, 1991.

    Google Scholar 

  91. Poddar S, Hong WK, Thacher SM, Lotan R. Suppression of type I transglutaminase, involucrin, and keratin K1 in cultured human head and neck squamous carcinoma 1483 cells by retinoic acid. Int J Cancer 48:239–247, 1991.

    PubMed  CAS  Google Scholar 

  92. Breitkreutz D, Boukamp P, Ryle CM, Stark HJ, Roop DR, Fusenig NE. Epidermal morphogenesis and keratin expression in c-Ha-ras-transfected tumorigenic clones of the human HaCaT cell line. Cancer Res 51:4402–4409, 1991.

    PubMed  CAS  Google Scholar 

  93. Agarwal C, Eckert RL. Immortalization of human keratinocytes by simian virus 40 large T antigen alters keratin gene response to retinoids. Cancer Res 50:5947–5953, 1990.

    PubMed  CAS  Google Scholar 

  94. Kaplan MJ, Mills SE, Rice RH, Johns ME. Involucrin in laryngeal dysplasia. Arch Otolaryngol 110:713–716, 1984.

    PubMed  CAS  Google Scholar 

  95. Said JW, Sassoon AF, Shintaku P, Banks-Schlegel S. Involucrin in squamous and basal cell carcinomas of the skin: An immunohistochemical study. J Invest Dermatol 82:449–552, 1984.

    PubMed  CAS  Google Scholar 

  96. Thacher SM, Coe EL, Rice RH. Retinoid suppression of transglutaminase activity and envelope competence in cultured human epidermal carcinoma cells. Differentiation 29: 82–87, 1985.

    PubMed  CAS  Google Scholar 

  97. Ta BM, Gallagher GT, Chakravarty R, Rice RH. Keratinocyte transglutaminase in human skin and oral mucosa: Cytoplasmic localization and uncoupling of differentiation markers. J Cell Sci 95:631–638, 1990.

    PubMed  CAS  Google Scholar 

  98. Levitt ML, Gazdar AF, Oie HK, Schuller H, Thacher SM. Cross-linked envelope-related markers for squamous differentiation in human hung cancer cell lines. Cancer Res 50:120–128, 1990.

    PubMed  CAS  Google Scholar 

  99. Cheng C, Kilkenny AE, Roop D, Yuspa SH. The v-Ha-ras oncogene inhibits the expression of differentiation markers and facilitates expression of cytokeratins 8 and 18 in mouse keratinocytes. Mol Carcinog 3:363–373, 1990.

    PubMed  CAS  Google Scholar 

  100. Nelson KG, Slaga TJ. Keratin modifications in epidermis, papillomas, and carcinomas during two-stage carcinogenesis in the SENCAR mouse. Cancer Res 43:4176–4181, 1982.

    Google Scholar 

  101. Weiss RA, Eichnerm R, Sun T-T. Monoclonal antibody analysis of keratin expression in epidermal diseases: 48-and 56-keratins as molecular markers for hyperproliferative keratinocytes. J Cell Biol 98:1397–1406, 1984.

    PubMed  CAS  Google Scholar 

  102. Toftgard R, Yuspa SH, Roop DR. Keratin gene expression in mouse skin tumors and in mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 45:5845–5850, 1985.

    PubMed  CAS  Google Scholar 

  103. Gimenez-Conti IB, Aldaz CM, Bianchi AB, Roop DR, Slaga TJ, Conti CJ. Early expression of type I K13 in the progression of mouse skin papillomas. Carcinogenesis 11:1995–1999, 1990.

    PubMed  CAS  Google Scholar 

  104. Kim KH, Schwartz F, Fuchs E. Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A. Proc Natl Acad Sci USA 81:4280–4284, 1984.

    PubMed  CAS  Google Scholar 

  105. Stoler A, Kopan R, Duvic M, Fuchs E. Use of monospecific antisera and cDNA probes to localize the major changes in keratin expression during normal and abnormal epidermal differentiation. J Cell Biol 107:427–446, 1988.

    PubMed  CAS  Google Scholar 

  106. Napoli JL, Race KR. The biosynthesis of retinoic acid from retinol by rat tissues in vitro. Arch Biochem Biophys 255:95–101, 1987.

    PubMed  CAS  Google Scholar 

  107. Napoli JL, Race KR. Biogenesis of retinoic acid from ß-carotene: Differences between the metabolism of ß-carotene and retinol. J Biol Chem 263:17372–17377, 1988.

    PubMed  CAS  Google Scholar 

  108. Napoli JL. The biogenesis of retinoic acid: A physiologically significant promoter of differentiation. In: MI Dawson, WH Nakamura, eds. Chemistry and Biology of Synthetic Retinoids. Boca Raton, FL: CRC Press, 1990, pp 229–249.

    Google Scholar 

  109. Siegenthaler G, Saurat J-H, Ponec M. The formation of retinoic acid from retinol in relation to the differentiation state of cultured human keratinocytes. Pharmacol Skin 3:52–55, 1989.

    Google Scholar 

  110. Connor MJ, Smith MH. The formation of all-trans-retinoic acid from all-trans retinol in hairless mouse skin. Biochem Pharmacol 36:919–924, 1987.

    PubMed  CAS  Google Scholar 

  111. Bhat PV, Jetten AM. Metabolism of all-trans-retinol and all-trans-retinoic acid in rabbit tracheal epithelial cells in culture. Biochim Biophys Acta 922:18–27, 1987.

    PubMed  CAS  Google Scholar 

  112. Seifter E, Rettura G, Padawer J, Levenson SM. Moloney murine sarcoma virus tumors in CBA/J mice: Chemopreventive and chemotherapeutic actions of supplemental ß-carotene. J Natl Cancer Inst 68:835–840, 1982.

    PubMed  CAS  Google Scholar 

  113. Som S, Chatterjee MM, Banerjee MR. ß-carotene inhibition of 7,12-dimethylbenz[a] anthracene-induced transformation of murine mammary cells in vitro. Carcinogenesis 5:937–940, 1984.

    PubMed  CAS  Google Scholar 

  114. Burton GW, Ingold KU. ß-carotene: An unusual type of lipid antioxidant. Science 224:569–573, 1984.

    PubMed  CAS  Google Scholar 

  115. Krinsky NI. Mechanism of inactivation of oxygen species by carotenoids. In: MG Simic, O Nygaard, eds. Anticarcinogenesis and Radiation Protection. New York: Plenum Press, 1988, pp 41–46.

    Google Scholar 

  116. Peto R, Doll R, Buckley JD, Sporn MB. Can dietary ß-carotene materially reduce human cancer rates? Nature 290:201–208, 1981.

    PubMed  CAS  Google Scholar 

  117. Krinsky NI. Evidence for the role of carotenoids in preventive health. Clin Nutr 7: 107–114, 1988.

    Google Scholar 

  118. Pung A, Rundhaug JE, Yoshizawa CN, Bertram JS. ß-carotene and canthaxanthine inhibit chemically-and physically-induced neoplastic transformation in 10T1/2 cells. Carcinogenesis 9:1533–1539, 1988.

    PubMed  CAS  Google Scholar 

  119. Tang G, Russell RM. 13-cis-retinoic acid is an endogenous compound in human serum. J Lipid Res 31:175–182, 1990.

    PubMed  CAS  Google Scholar 

  120. Moon RC, Mehta RC. Retinoid inhibition of experimental carcinogenesis. In: MI Dawson, WH Okamura, eds. Chemistry and Biology of Synthetic Retinoids. Boca Raton, FL: CRC Press, 1990, pp 501–518.

    Google Scholar 

  121. Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A, Grippo JF. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα. Nature 335: 359, 1992.

    Google Scholar 

  122. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C. 9-cis retinoic acid is a high-affinity ligand for the retinoid X receptor. Cell 68:397–406, 1992.

    PubMed  CAS  Google Scholar 

  123. Eichner R. Epidermal effects of retinoids: In vitro studies. J Am Acad Dermatol 15:789–797, 1986.

    PubMed  CAS  Google Scholar 

  124. Varani J, Nockoloff BJ, Dixit VM, Mitra RS, Voorhees JJ. All-trans-retinoic acid stimulates growth of adult keratinocytes cultured in growth factor-deficient medium, inhibits production of thrombospondin and fibronectin, and reduces adhesion. J Invest Dermatol 93:449–454, 1989.

    PubMed  CAS  Google Scholar 

  125. Tong PS, Horowitz NN, Wheeler LA. Trans retinoic acid enhances the growth response of epidermal keratinocytes to epidermal growth factor and transforming growth factor beta. J Invest Dermatol 94:126–131, 1990.

    PubMed  CAS  Google Scholar 

  126. McDowell EM, Ben T, Colemen B, Chang S, Newkirk C, De Luca LM. Effects of retinoic acid on the growth and morphology of hamster tracheal epithelial cells in primary culture. Virchows Arch [Cell Pathol] 54:38–51, 1987.

    CAS  Google Scholar 

  127. Choi Y, Fuchs E. TGF-ß and retinoic acid: Regulators of growth and modifiers of differentiation in human epidermis. Cell Regul 1:791–809, 1990.

    PubMed  CAS  Google Scholar 

  128. Lotan R, Lotan D, Sacks PG. Inhibition of tumor cell growth by retinoids. Methods Enzymol 190:100–110, 1990.

    PubMed  CAS  Google Scholar 

  129. Frey JR, Peck R, Bollag W. Antiproliferative activity of retinoids, interferon α and their combination in five human transformed cell lines. Cancer Lett 57:223–227, 1991.

    PubMed  CAS  Google Scholar 

  130. Lotan R, Sacks PG, Lotan D, Hong WK. Differential effects of retinoic acid on the in vitro growth and cell-surface glycoconjugates of two human head and neck squamous-cell carcinomas. Int J Cancer 40:224–229, 1987.

    PubMed  CAS  Google Scholar 

  131. Sacks PG, Oke V, Vasey T, Lotan R. Modulation of growth, differentiation, and glycoprotein synthesis by ß-all-trans retinoic acid in a multicellular tumor spheroid model for squamous carcinoma of the head and neck. Int J Cancer 44:926–933, 1989.

    PubMed  CAS  Google Scholar 

  132. Pirisi L, Batova A, Jenkins GR, Hodam JR, Creek KE. Increased sensitivity of human keratinocytes immortalized by human papillomavirus type 16 DNA to growth control by retinoids. Cancer Res 52:187–193, 1992.

    PubMed  CAS  Google Scholar 

  133. Tong PS, Mayes DM, Wheeler LA. Differential effects of retinoids on DNA synthesis in calcium-regulated murine epidermal keratinocyte cultures. J Invest Dermatol 90:861–868, 1988.

    PubMed  CAS  Google Scholar 

  134. Glick AB, Flanders KC, Danielpour D, Yuspa SH, Sporn MB. Retinoic acid induces transforming growth factor-beta2 in cultured keratinocytes and mouse epidermis. Cell Regul 1:87–97, 1989.

    PubMed  CAS  Google Scholar 

  135. Kim JS, Steck PA, Gallick GE, Lee JS, Blick M, Hong WK, Lotan R. Suppression by retinoic acid of epidermal growth factor receptor autophosphorylation and glycosylation in cultured human head and neck squamous carcinoma cells. Monogr Natl Cancer Inst 13:101–110, 1992.

    PubMed  Google Scholar 

  136. Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R, Fofonoff S, Byers R, Atkinson EN, Vaughan C, Toth BB, Kramer A, Dimery IW, Skipper P, Strong S. The efficacy of 13-cis retinoic acid in the treatment of oral leukoplakia. N Engl J Med 315:1501–1505, 1986.

    PubMed  CAS  Google Scholar 

  137. Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, Schantz SS, Kramer AM, Lotan R, Peters LL Dimery IW, Brown BW, Goepfert H. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323:795–801, 1990.

    PubMed  CAS  Google Scholar 

  138. Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 318:1633–1637, 1988.

    PubMed  CAS  Google Scholar 

  139. Lippman S, Kessler JF, Meyskens F Jr. Retinoids as preventive and therapeutic anticancer agents. Cancer Treat Rep 71:391–405 (Part 1); 493–515 (Part 2), 1987.

    PubMed  CAS  Google Scholar 

  140. Lippman SM, Hong WK. Prevention of aerodigestive cancers with retinoids. Cancer Bull 43:525–533, 1991.

    Google Scholar 

  141. Lippman SM, Meyskens FL. Results of the use of vitamin A and retinoids in cutaneous malignancies. Pharmacol Ther 40:107–122, 1989.

    PubMed  CAS  Google Scholar 

  142. Smith MA, Parkinson DR, Cheson BD, Friedman MA. Retinoids in cancer therapy. J Clin Oncol 10:839–864, 1992.

    PubMed  CAS  Google Scholar 

  143. Nagae S, Lichti U, DeLuca LM, Yuspa SH. Effect of retinoic acid on cornified envelope formation: Difference between spontaneous envelope formation in vivo or in vitro. J Invest Dermatol 89:51–58, 1987.

    PubMed  CAS  Google Scholar 

  144. Floyd EE, Jetten AM. Regulation of type I (epidermal) transglutaminase mRNA levels during squamous differentiation: Down regulation by retinoids. Mol Cell Biol 9:4846–4851, 1989.

    PubMed  CAS  Google Scholar 

  145. Rubin AL, Rice RH. Differential regulation by retinoic acid and calcium of transglutaminases in cultured neoplastic and normal human keratinocytes. Cancer Res 46:2356–2361, 1986.

    PubMed  CAS  Google Scholar 

  146. Rubin AL, Parenteau NL, Rice RH. Coordination of keratinocyte programming in human SCC-13 squamous carcinoma and normal epidermal cells. J Cell Physiol 138:208–214, 1989.

    PubMed  CAS  Google Scholar 

  147. Hohl D, Lichti U, Breitkreutz D, Steinert PM, Roop D. Transcription of the human loricrin gene in vitro is induced by calcium and cell density and suppressed by retinoic acid. J Invest Dermatol 96:414–418, 1991.

    PubMed  CAS  Google Scholar 

  148. Magnaldo T, Pommes L, Asselineau D, Darmon M. Isolation of a GC-rich cDNA identifying mRNA present in human epidermis and modulated by calcium and retinoic acid in cultured keratinocytes. Mol Biol Rep 14:237–246, 1990.

    PubMed  CAS  Google Scholar 

  149. Smits HL, Floyd EE, Jetten AM. Molecular cloning of gene sequences regulated during squamous differentiation of tracheal epithelial cells and controlled by retinoic acid. Mol Cell Biol 7:4017–4023, 1987.

    PubMed  CAS  Google Scholar 

  150. Gorodeski GI, Eckert RL, Utian WH, Sheean L, Rorke EA. Retinoids, sex steroids, and glucocorticoids regulate ectocervical cell envelope formation but not the level of the envelope precursor, involucrin. Differentiation 42:75–80, 1989.

    PubMed  CAS  Google Scholar 

  151. Rice RH, Cline PR, Coe EL. Mutually antagonistic effects of hydrocortisone and retinyl acetate on envelope competence in cultured malignant human keratinocytes. J Invest Dermatol 81:176s–178s, 1983.

    PubMed  CAS  Google Scholar 

  152. Michel S, Reichert U, Isnard JL, Shroot B, Schmidt R. Retinoic acid controls expression of epidermal transglutaminase at the pre-translational level. FEBS Lett 258:35–38, 1989.

    PubMed  CAS  Google Scholar 

  153. Regnier M, Darmon M. Human epidermis reconstructed in vitro: A model to study keratinocyte differentiation and its modulation by retinoic acid. In Vitro 25:1000–1008, 1989.

    CAS  Google Scholar 

  154. Tseng SCG, Hatchell D, Tierney N, Huang AJ-W, Sun T-T. Expression of specific keratin markers by rabbit corneal, conjunctival, and esophageal epithelia during vitamin A deficiency. J Cell Biol 99:2279–2286, 1984.

    PubMed  CAS  Google Scholar 

  155. Huang FL, Roop DR, DeLuca LM. Vitamin A deficiency and keratin biosynthesis in cultured hamster trachea. In Vitro Cell Dev Biol 22:223–230, 1986.

    PubMed  CAS  Google Scholar 

  156. Fuchs E, Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell 25:617–625, 1981.

    PubMed  CAS  Google Scholar 

  157. Gilfix BM, Green H. Bioassay of retinoids using cultured human conjunctival keratinocytes. J Cell Physiol 119:172–174, 1984.

    PubMed  CAS  Google Scholar 

  158. Gilfix BM, Eckert RL. Coordinate control by vitamin A of keratin gene expression in human keratinocytes. J Biol Chem 260:14026–14029, 1985.

    PubMed  CAS  Google Scholar 

  159. Eckert RL, Green H. Cloning of cDNAs specifying vitamin A-responsive human keratins. Proc Natl Acad Sci USA 81:4321–4325, 1984.

    PubMed  CAS  Google Scholar 

  160. Terasaki T, Shimosato Y, Nakajima T, Tsumuraya M, Ichinose H, Nagatsu T, Kato K. Reversible squamous cell characteristics induced by vitamin A deficiency in a small cell lung cancer cell line. Cancer Res 47:3533–3537, 1987.

    PubMed  CAS  Google Scholar 

  161. Kopan R, Traska G, Fuchs E. Retinoids as important regulators of terminal differentiation: Examining keratin expression in individual epidermal cells at various stages of keratinization. J Cell Biol 105:427–440, 1987.

    PubMed  CAS  Google Scholar 

  162. Mendelsohn MG, DiLorenzo TP, Abramson AL, Steinberg BM. Retinoic acid regulates, in vitro, the two normal pathways of differentiation of human laryngeal keratinocytes. In Vitro Cell Dev Biol 27A:137–141, 1991.

    PubMed  CAS  Google Scholar 

  163. Reppucci AD, DiLorenzo TP, Abramson AL, Steinberg BM. In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid. Otolaryngol Head Neck Surg 105:528–532, 1991.

    PubMed  CAS  Google Scholar 

  164. Asselineau D, Dale BA, Bernard BA. Filaggrin production by cultured human epidermal keratinocytes and its regulation by retinoic acid. Differentiation 45:221–229, 1990.

    PubMed  CAS  Google Scholar 

  165. Rosenthal DS, Griffiths CE, Yuspa SH, Roop DR, Voorhees JJ. Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14. J Invest Dermatol 98:343–350, 1992.

    PubMed  CAS  Google Scholar 

  166. Griffiths CE, Rosenthal DS, Reddy AP, Elder JT, Astrom A, Leach K, Wang TS, Finkel LJ, Yuspa SH, Voorhees JJ, Fisher GJ. Short-term retinoic acid treatment increases in vivo, but decreases in vitro, epidermal transglutaminase-K enzyme activity and imunoreactivity. J Invest Dermatol 99:283–288, 1992.

    PubMed  CAS  Google Scholar 

  167. Chytil F, Ong D. Cellular retinoid-binding proteins. In: MB Sporn, AB Roberts, DS Goodman, eds. The Retinoids. New York: Academic Press, 1984, pp 90–123.

    Google Scholar 

  168. Wolf G. The intracellular vitamin A-binding proteins: An overview of their functions. Nutr Rev 49:1–12, 1991.

    PubMed  CAS  Google Scholar 

  169. Mangelsdorf DJ, Evans RM. Vitamin A receptors: New insights on retinoid control of transcription. In: G Morriss-Kay, ed. Retinoids in Normal Development and Terato-genesis. New York: Oxford University Press, 1992, pp 27–50.

    Google Scholar 

  170. Lotan R, Clifford JL. Nuclear receptors for retinoids: Mediators of retinoid effects on normal and malignant cells. Biomed Pharmocother 45:145–156, 1990.

    Google Scholar 

  171. Siegenthaler G, Saurat J-H, Morin C, Hotz R. Cellular retinol and retinoic acid-binding proteins in the epidermis and dermis of normal human skin. Br J Dermatol 111:647–654, 1984.

    PubMed  CAS  Google Scholar 

  172. Siegenthaler G, Samson J, Bernard JP, Fiore-Donno G, Saurat JH. Retinoid-binding proteins in human oral mucosa. J Oral Pathol 17:106–112, 1988.

    PubMed  CAS  Google Scholar 

  173. Siegenthaler G, Saurat J-H, Ponec M. Terminal differentiation in cultured human keratinocytes is associated with increased levels of cellular retinoic acid-binding protein. Exp Cell Res 178:114–126, 1988.

    PubMed  CAS  Google Scholar 

  174. Siegenthaler G, Saurat J-H, Hotz R, Camenzind M, Merot Y. Cellular retinoic acid, but not cellular retinol-binding protein, is elevated in psoriatic plaques. J Invest Dermatol 86:42–45, 1984.

    Google Scholar 

  175. Siegenthaler G, Saurat J-H. Plasma and skin carriers for natural and synthetic retinoids. Arch Dermatol 123:1690–1692, 1987.

    Google Scholar 

  176. Hirschel-Scholz S, Siegenthaler G, Saurat J-H. Ligand-specific and nonspecific in vivo modulation of human epidermal cellular retinoic acid binding protein (CRABP). Eur J Clin Invest 19:220–227, 1989.

    PubMed  CAS  Google Scholar 

  177. Gates RE, Maytield C, Allred LE. Human neonatal keratinocytes have very high levels of cellular vitamin A-binding proteins. J Invest Dermatol 88:37–41, 1987.

    PubMed  CAS  Google Scholar 

  178. Bailey JS, Siu CH. Purification and partial characterization of a novel binding protein from the neonatal rat. J Biol Chem 263:9326–9332, 1988.

    PubMed  CAS  Google Scholar 

  179. Giguere V, Lyn S, Yip P, Siu C-H, Amin S. Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein. Proc Natl Acad Sci USA 87:6233–6237, 1990.

    PubMed  CAS  Google Scholar 

  180. Astrom A, Tavakkol A, Pettersson U, Cromie M, Elder JT, Voorhees JJ. Molecular cloning of two human cellular retinoic acid-binding proteins (CRABP). J Biol Chem 266:17662–17666, 1991.

    PubMed  CAS  Google Scholar 

  181. Eller MS, Oleksiak MF, McQuaid TJ, McAfee SG, Gilchrest BA. The molecular cloning and expression of two CRABP cDNAs from human skin. Exp Cell Res 199:328–336, 1992.

    Google Scholar 

  182. Ong DE, Goodwin WJ, Jesse RH, Griffin AC. Presence of cellular retinol and retinoic acid-binding proteins in epidermoid carcinoma of the oral cavity and oropharynx. Cancer 49:1409–1412, 1982.

    PubMed  CAS  Google Scholar 

  183. Gates RE, Rees RS. Altered vitamin A-binding proteins in carcinoma of the head and neck. Cancer 56:2598–2604, 1985.

    PubMed  CAS  Google Scholar 

  184. Rallet A, Jardillier JC. Cellular binding proteins for retinol and retinoic acid in head and neck carcinomas and in human breast cancer cell lines. Steroids 52:397–398, 1988.

    PubMed  CAS  Google Scholar 

  185. Fex G, Wahlberg P, Biorklund A, Wennerberg J, Willen R. Studies of cellular retinol-binding protein (CRBP) in squamous-cell carcinomas of the head and neck region. Int J Cancer 37:217–221, 1986.

    PubMed  CAS  Google Scholar 

  186. Yanagita T, Komiyama S, Kuwano M. Cellular retinol-binding proteins in head and neck tumors and their adjacent tissues. Cancer 58:2251–2255, 1986.

    PubMed  CAS  Google Scholar 

  187. Wahlberg P, Fex G, Biorklund A, Trope C, Willen R. Quantitation and localization of cellular retinol-binding protein in squamous cell carcinomas of the cervix uteri and of the oral cavity. Int J Cancer 41:771–776, 1988.

    PubMed  CAS  Google Scholar 

  188. Zou C-P, Clifford J, Xu X-C, Sacks P, Jetten A, Eckert R, Roop D, Chambon P, Hong K, Lotan R. Expression of differentiation markers, retinoic acid-binding proteins and nuclear receptors in human head and neck carcinoma cells and their modulation by retinoic acid. Proc Am Assoc Cancer Res 1993, in press.

    Google Scholar 

  189. Takase S, Ong DE, Chytil F. Cellular retinol-binding protein allows specific interaction of retinol with the nucleus in vitro. Proc Natl Acad Sci USA 76:2204–2208, 1979.

    PubMed  CAS  Google Scholar 

  190. Takase S, Ong DE, Chytil F. Transfer of retinoic acid from its complex with cellular retinoic acid-binding protein to the nucleus. Arch Biochem Biophys 247:328–334, 1986.

    PubMed  CAS  Google Scholar 

  191. Maden M, Ong DE, Summerbell D, Chytil F. Spatial distribution of cellular protein binding to retinoic acid in the chick limb bud. Nature 335:733–735, 1988.

    PubMed  CAS  Google Scholar 

  192. Boylan JF, Gudas JI. Overexpression of the cellular retinoic acid binding protein-I (CRABP-I) results in reduction in differentiation-specific gene expression in F9 teratocar-cinoma cells. J Cell Biol 112:965–979, 1991.

    PubMed  CAS  Google Scholar 

  193. Lotan R, Ong DE, Chytil F. Comparison of the level of cellular retinoid-binding proteins and susceptibility to retinoid-induced growth inhibition of various neoplastic cell lines. J Natl Cancer Inst 64:1259–1262, 1980.

    PubMed  CAS  Google Scholar 

  194. Lotan R, Stolarsky T, Lotan D. Isolation and analysis of melanoma cell mutants resistant to the antiproliferative action of retinoic acid. Cancer Res 43:2868–2875, 1983.

    PubMed  CAS  Google Scholar 

  195. Jetten AM, Anderson K, Deas MA, Kagechika H, Lotan R, Rearick JI, Shudo K. New benzoic acid derivatives with retinoid activity: Lack of direct correlation between biological activity and binding to CRABP. Cancer Res 47:3523–3527, 1987.

    PubMed  CAS  Google Scholar 

  196. Asselineau D, Cavey M-T, Shroot B, Darmon M. Control of epidermal differentiation by a retinoid analogue unable to bind to cytosolic retinoic acid-binding proteins (CRABP). J Invest Dermatol 98:128–134, 1992.

    PubMed  CAS  Google Scholar 

  197. Boylan JF, Gudas JL. The level of CRABP-I expression influences the amounts and types of all-trans-retinoic acid metabolites in F9 teratocarcinoma cells. J Biol Chem 267:21486–21491, 1992.

    PubMed  CAS  Google Scholar 

  198. Glass CK, DiRenzo J, Kurokawa R, Han Z. Regulation of gene expression by retinoic acid receptors. DNA Cell Biol 10:623–638, 1991.

    PubMed  CAS  Google Scholar 

  199. Leid M, Kastner P, Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci 17:427–433, 1992.

    PubMed  CAS  Google Scholar 

  200. Petkovich M, Brand NJ, Krust A, Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330:444–450, 1987.

    PubMed  CAS  Google Scholar 

  201. Giguere V, Ong ES, Segui P, Evans RM. Identification of a receptor for the morphogen retinoic acid. Nature 330:624–629, 1987.

    PubMed  CAS  Google Scholar 

  202. Brand N, Petkovich M, Krust A, Chambon P, de The H, Marchio A, Tiollas P, Dejean A. Identification of a second human retinoic acid receptor. Nature 332:850–853, 1988.

    PubMed  CAS  Google Scholar 

  203. Benbrook D, Lernhardt E, Pfahl M. A new retinoic acid receptor identified from a hepatocellular carcinoma. Nature 33:669–672, 1988.

    Google Scholar 

  204. Krust A, Kastner P, Petkovich M, Zelent A, Chambon P. A third human retinoic acid receptor, hRAR-g. Proc Natl Acad Sci USA 86:5310–5314, 1989.

    PubMed  CAS  Google Scholar 

  205. Ishikawa T, Umesono K, Mangelsdorf DJ, Aburatani H, Stanger BZ, Shibasaki Y, Imawari M, Evans RM, Takaku F. A functional retinoic acid receptor encoded by the gene on human chromosome 12. Mol Endocrinol 4:837–844, 1990.

    PubMed  CAS  Google Scholar 

  206. Kastner P, Krust A, Mendelsohn C, Gamier JM, Zelent A, Leroy P, Staub A, Chambon P. Murine forms of retinoic acid receptor γ with specific patterns of expression. Proc Natl Acad Sci USA 87:2700–2704, 1990.

    PubMed  CAS  Google Scholar 

  207. Mattei MG, Petkovich M, Mattei JF, Brand N, Chambon P. Mapping of the human retinoic acid receptor to the q21 band of chromosome 17. Hum Genet 80:186–188, 1988.

    PubMed  CAS  Google Scholar 

  208. Mattei MG, de The H, Mattei JF, Marchio A, Tiollais P, Dejean A. Assignment of the human hap retinoic acid receptor RAR-beta gene to the p24 band of chromosome 3. Hum Genet 80:189–190, 1988.

    PubMed  CAS  Google Scholar 

  209. Brockes JP. Retinoids, homeobox genes, and limb morphogenesis. Neuron 2:1285–1294, 1989.

    PubMed  CAS  Google Scholar 

  210. Ruberte E, Dolle P, Krust A, Zelent A, Morris-Kay G, Chambon P. Special and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryo-genesis. Development 108: 213–222, 1990.

    PubMed  CAS  Google Scholar 

  211. Dolle P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P. Differential expression of genes encoding α, β, and γ retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 342:702–705, 1989.

    PubMed  CAS  Google Scholar 

  212. Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345:224–229, 1990.

    PubMed  CAS  Google Scholar 

  213. Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 6:329–344, 1992.

    PubMed  CAS  Google Scholar 

  214. Yu VC, Delsert C, Andersen B, Holloway JW, Devary OV, Naar AM, Kim SY, Boutin J-M, Glass CK, Rosenfeld MG. RXRß: A coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell 67:1251–1266, 1991.

    PubMed  CAS  Google Scholar 

  215. Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355:446–449, 1992.

    PubMed  CAS  Google Scholar 

  216. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen J-Y, Staub A, Gamier J-M, Mader S, Chambon P. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68:377–395, 1992.

    PubMed  CAS  Google Scholar 

  217. Zhang X-K, Hoffmann B, Tran PB-V, Graupner G, Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature 355:441–446, 1992.

    PubMed  CAS  Google Scholar 

  218. de The H, Vivanco-Ruiz MdM, Tiollais P, Stunnenberg H, Dejean A. Identification of a retinoic acid responsive element in the retinoic acid receptor β gene. Nature 343:177–180, 1990.

    PubMed  Google Scholar 

  219. Sucov HM, Murakami KK, Evans RM. Characterization of an autoregulated response element in the mouse retinoic acid receptor type β gene. Proc Natl Acad Sci USA 87:5392–5396, 1990.

    PubMed  CAS  Google Scholar 

  220. Umesono K, Murakami KK, Thompson CC, Evans RM. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65:1255–1266, 1991.

    PubMed  CAS  Google Scholar 

  221. Leroy P, Krust A, Zelent A, Mendelsohn C, Garnier J-M, Kastner P, Dierich A, Chambon P. Multiple isoforms of the mouse retinoic acid receptor α are generated by alternative splicing and differential induction by retinoic acid. EMBO J 10:59–69, 1991.

    PubMed  CAS  Google Scholar 

  222. Lehmann JM, Zhang X-K, Pfahl M. RARγ2 expression is regulated through a retinoic acid response element embedded in Spl sites. Mol Cell Biol 12:2976–2985, 1992.

    PubMed  CAS  Google Scholar 

  223. Vasios GW, Gold JD, Petkovich M, Chambon P, Gudas LJ. A retinoic acid-responsive element is present in the 5’ flanking region of the laminin Bl gene. Proc Natl Acad Sci USA 86:9099–9103, 1989.

    PubMed  CAS  Google Scholar 

  224. Schule R, Umesono K, Mangelsdorf DJ, Bolado J, Pike W, Evans RM. Jun-fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene. Cell 61:497–504, 1990.

    PubMed  CAS  Google Scholar 

  225. Munoz-Canoves P, Vik D, Tack B. Mapping of a retinoic acid-responsive element in the promotor region of the complement factor H gene. J Biol Chem 265:20065–20068, 1990.

    PubMed  CAS  Google Scholar 

  226. Duester G, Shean M, McBride MS, Stewart MJ. Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: Implications for regulation of retinoic acid synthesis. Mol Cell Biol 11:1638–1646, 1991.

    PubMed  CAS  Google Scholar 

  227. Richard S, Zingg HH. Identification of a retinoic acid response element in the human oxytocin promotor. J Biol Chem 266:21428–21433, 1991.

    PubMed  CAS  Google Scholar 

  228. Arcioni L, Simeone A, Guazzi S, Zappavigna V, Boncinelli E, Mavilio F. The upstream region of the human homeobox gene HOX3D is a target for regulation by retinoic acid and HOX homeoproteins. EMBO J 11:265–277, 1992.

    PubMed  CAS  Google Scholar 

  229. Durand B, Saunders M, Leroy P, Leid M, Chambon P. All-trans and 9-cis retinoic acid induction of mouse CRABP-II gene transcription is mediated by RAR/RXR heterodimers bound to DR1 and DR2 directly repeated motifs. Cell 71:73–85, 1992.

    PubMed  CAS  Google Scholar 

  230. Rottman JN, Widom RL, Nadal-Ginard B, Mahdavi V, Karathanasis SK. A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways. Mol Cell Biol 11:3814–3820, 1991.

    PubMed  CAS  Google Scholar 

  231. Mangelsdorf DJ, Umesono K, Kliewer SA, Borgmeyer U, Ong ES, Evans RM. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR. Cell 66:555–561, 1991.

    PubMed  CAS  Google Scholar 

  232. Raisher BD, Gulick T, Zhang Z, Strauss AW, Moore DD, Kelly DP. Identification of a novel retinoid-responsive element in the promoter region of the medium chain acyl-coenzyme A dehydrogenase gene. J Biol Chem 267:20264–20269, 1992.

    PubMed  CAS  Google Scholar 

  233. Zhang X-K, Hoffmann B, Tran PB-V, Graupner G, Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature 355:441–446, 1992.

    PubMed  CAS  Google Scholar 

  234. Nicholson RC, Mader S, Nagpal S, Leid M, Rochette-Egly C, Chambon P. Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site. EMBO J 9:4443–4454, 1990.

    PubMed  CAS  Google Scholar 

  235. Schule R, Rangarajan P, Yang N, Kliewer S, Ransone L, Bolado J, Verma IM, Evans RM. Retinoic acid is a negative regulator of AP-1 responsive genes. Proc Natl Acad Sci USA 88:6092–6096, 1991.

    PubMed  CAS  Google Scholar 

  236. Zelent A, Krust A, Petkovich M, Kastner P, Chambon P. Cloning of murine α and β retinoic acid receptors and a novel receptor γ predominantly expressed in skin. Nature 339:714–717, 1989.

    PubMed  CAS  Google Scholar 

  237. Rees JL, Redfern CPE. Expression of the α and β retinoic acid receptors in skin. J Invest Dermatol 93:818–820, 1989.

    PubMed  CAS  Google Scholar 

  238. Dolle P, Ruberte E, Laroy P, Morris-Kay G, Chambon P. Retinoic acid receptors and cellular binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development 110:1133–1151, 1990.

    PubMed  CAS  Google Scholar 

  239. Elder JT, Fisher GJ, Zhang Q-Y, Eisen D, Krust A, Kastner P, Chambon P, Voorhees JJ. Retinoic acid receptor gene expression in human skin. J Invest Dermatol 96:425–433, 1991.

    PubMed  CAS  Google Scholar 

  240. Redfern CPF, Todd C. Retinoic acid receptor expression in human skin keratinocytes and dermal fibroblasts in vitro. J Cell Sci 102:113–121, 1992.

    PubMed  CAS  Google Scholar 

  241. Vollberg TM, Nervi C, George MD, Fujimoto W, Krust A, Jetten AM. Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation. Mol Endocrinol 6:667–676, 1992.

    PubMed  CAS  Google Scholar 

  242. Fujimoto W. Expression pattern of retinoic acid receptor genes in normal human skin. Jpn J Dermatol 100:1227–1233, 1990.

    CAS  Google Scholar 

  243. Finzi E, Blake MJ, Celano P, Skouge J, Diwan R. Cellular localization of retinoic acid receptor-gamma expression in normal and neoplastic skin. Am J Pathol 140:1463–1471, 1992.

    PubMed  CAS  Google Scholar 

  244. Crowe DL, Hu L, Gudas LJ, Rheinwald JG. Variable expression of retinoic acid receptor (RAR beta) mRNA in human oral and epidermal keratinocytes; relation to keratin 19 expression and keratinization potential. Differentiation 48:199–208, 1991.

    PubMed  CAS  Google Scholar 

  245. Nervi C, Vollberg TM, George MD, Zelent A, Chambon P, Jetten AM. Expression of nuclear retinoic acid receptors in normal tracheobronchial cells and in lung carcinoma cells. Exp Cell Res 195:163–70, 1991.

    PubMed  CAS  Google Scholar 

  246. Gebert JF, Moghal N, Frangioni JV, Sugarbaker DJ, Neel BG. High frequency of retinoic acid receptor beta abnormalities in human lung cancer. Oncogene 6:1859–1868, 1991.

    PubMed  CAS  Google Scholar 

  247. Hu L, Crowe DL, Rheinwald JG, Chambon P, Gudas LJ. Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res 51:3972–3981, 1991.

    PubMed  CAS  Google Scholar 

  248. Xu X-C, Ro JY, Lee JS, Shin DM, Hittelman WN, Lippman SM, Toth BB, Martin JW, Hong WK, Lotan R. Differential expression of nuclear retinoic acid receptors in surgical specimens from head and neck ‘normal’, hyperplastic, premalignant and malignant tissues. Proc Am Assoc Cancer Res 34:3285, 1993.

    Google Scholar 

  249. Latif F, Fivash M, Glenn G, Tory K, Orcutt ML, Hampsch K, Delisio J, Lerman M, Cowan J, Beckett M, Weichselbaum R. Chromosome 3p deletions in head and neck carcinomas: Statistical ascertainment of allelic loss. Cancer Res 52:1451–1456, 1992.

    PubMed  CAS  Google Scholar 

  250. Houle B, Leduc F, Bradley WEC. Implication of RARB in epidermoid (squamous) lung cancer. Genes Chromosom Cancer 3:358–366, 1991.

    PubMed  CAS  Google Scholar 

  251. Brauch H, Johnson B, Hovis J, Yano T, Gazdar Y, Fettengill OS, Graziano S, Sorensen OD, Poiesz BJ, Minna J, Linehan WM, Zbar B. Molecular analysis of the short arm of chromosome 3 in small cell and non-small cell carcinomas of the lung. N Engl J Med 317:1109–1113, 1987.

    PubMed  CAS  Google Scholar 

  252. Naylor SL, Bishop DT. Report of the Committee on the Genetic Constitution of Chromosome 3 (HGM 10). Cytogenet Cell Genet 51:106–120, 1989.

    PubMed  CAS  Google Scholar 

  253. Albertson DG, Sherrington PD, Rabbits PH. Localization of polymorphic DNA probes frequently deleted in lung carcinoma. Hum Genet 83:127–132, 1989.

    PubMed  CAS  Google Scholar 

  254. Espeseth AS, Murphy SP, Linney E. Retinoic acid receptor expression vector inhibits differentiation of F9 embryonal carcinoma cells. Genes Dev 3:1647–1656, 1989.

    PubMed  CAS  Google Scholar 

  255. Cope FO, Wille JJ. Retinoid receptor antisense DNAs inhibit alkaline phosphatase induction and clonogenicity in malignant keratinocytes. Proc Natl Acad Sci USA 86: 5590–5594, 1989.

    PubMed  CAS  Google Scholar 

  256. Collins SJ, Robertson KA, Mueller L. Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-α). Mol Cell Biol 10:2154–2163, 1990.

    PubMed  CAS  Google Scholar 

  257. Robertson KA, Emami B, Mueller L, Collins SJ. Multiple members of the retinoic acid receptor family are capable of mediating the granulocytic differentiation of HL-60 cells. Mol Cell Biol 12:3743–3749, 1992.

    PubMed  CAS  Google Scholar 

  258. Robertson KA, Mueller L, Collins SJ. Retinoic acid receptors in myeloid leukemia: Characterization of receptors in retinoic acid-resistant K-562 cells. Blood 77:340–347, 1991.

    PubMed  CAS  Google Scholar 

  259. Stellmach V, Leask A, Fuchs E. Retinoid-mediated transcriptional regulation of keratin genes in human epidermal and squamous cell carcinoma cells. Proc Natl Acad Sci USA 88:4582–4596, 1991.

    PubMed  CAS  Google Scholar 

  260. Tomic M, Jiang CK, Epstein HS, Freedberg IM, Samuels HH, Blumenberg M. Nuclear receptors for retinoic acid and thyroid hormone regulate transcription of keratins. Cell Regul 1:965–973, 1990.

    PubMed  CAS  Google Scholar 

  261. Aneskievich BJ, Fuchs E. Teminal differentiation in keratinocytes involves positive as well as negative regulation by retinoic acid receptors and retinoid X receptors at retinoid response elements. Mol Cell Biol 12:4862–4871, 1992.

    PubMed  CAS  Google Scholar 

  262. Leroy P, Krust A, Kastner P, Mendelsohn C, Zelent A, Chambon P. Retinoic acid receptors. In: G Morriss-Kay, ed. Retinoids in Normal Development and Teratogenesis. New York: Oxford University Press, 1992, pp 7–25.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Lotan, R.M. (1995). Squamous differentiation and retinoids. In: Hong, W.K., Weber, R.S. (eds) Head and Neck Cancer. Cancer Treatment and Research, vol 74. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2023-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-2023-8_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5837-4

  • Online ISBN: 978-1-4615-2023-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics