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Epigenetic Gene Silencing in Prostate Cancer

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Prostate Cancer

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References

  1. Feinberg, A. P., Cui, H., and Ohlsson, R. DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms. Semin Cancer Biol, 12: 389–398, 2002.

    Article  PubMed  CAS  Google Scholar 

  2. Onyango, P., Jiang, S., Uejima, H., Shamblott, M. J., Gearhart, J. D., Cui, H., and Feinberg, A. P. Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages. Proc Natl Acad Sci USA, 99: 10599–10604, 2002.

    Article  PubMed  CAS  Google Scholar 

  3. Tilghman, S. M. The sins of the fathers and mothers: genomic imprinting in mammalian development. Cell, 96: 185–193, 1999.

    Article  PubMed  CAS  Google Scholar 

  4. Norris, D. P., Brockdorff, N., and Rastan, S. Methylation status of CpG-rich islands on active and inactive mouse X chromosomes. Mamm Genome, 1: 78–83, 1991.

    Article  PubMed  CAS  Google Scholar 

  5. Challita, P. M., Skelton, D., el-Khoueiry, A., Yu, X. J., Weinberg, K., and Kohn, D. B. Multiple modifications in cis elements of the long terminal repeat of retroviral vectors lead to increased expression and decreased DNA methylation in embryonic carcinoma cells. J Virol, 69: 748–755, 1995.

    PubMed  CAS  Google Scholar 

  6. Shinar, D., Yoffe, O., Shani, M., and Yaffe, D. Regulated expression of muscle-specific genes introduced into mouse embryonal stem cells: inverse correlation with DNA methylation. Differentiation, 41: 116–126, 1989.

    Article  PubMed  CAS  Google Scholar 

  7. Chapman, V., Forrester, L., Sanford, J., Hastie, N., and Rossant, J. Cell lineage-specific undermethylation of mouse repetitive DNA. Nature, 307: 284–286, 1984.

    Article  PubMed  CAS  Google Scholar 

  8. Tolberg, M. E., Funderburk, S. J., Klisak, I., and Smith, S. S. Structural organization and DNA methylation patterning within the mouse L1 family. J Biol Chem, 262: 11167–11175, 1987.

    PubMed  CAS  Google Scholar 

  9. Razin, A. and Riggs, A. D. DNA methylation and gene function. Science, 210: 604–610, 1980.

    Article  PubMed  CAS  Google Scholar 

  10. Siegfried, Z. and Cedar, H. DNA methylation: a molecular lock. Curr Biol, 7: R305–307, 1997.

    Article  PubMed  CAS  Google Scholar 

  11. Siegfried, Z., Eden, S., Mendelsohn, M., Feng, X., Tsuberi, B. Z., and Cedar, H. DNA methylation represses transcription in vivo. Nat Genet, 22: 203–206, 1999.

    Article  PubMed  CAS  Google Scholar 

  12. Santos, F., Hendrich, B., Reik, W., and Dean, W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol, 241: 172–182, 2002.

    Article  PubMed  CAS  Google Scholar 

  13. Rainier, S., Johnson, L. A., Dobry, C. J., Ping, A. J., Grundy, P. E., and Feinberg, A. P. Relaxation of imprinted genes in human cancer. Nature, 362: 747–749, 1993.

    Article  PubMed  CAS  Google Scholar 

  14. Jarrard, D. F., Bussemakers, M. J., Bova, G. S., and Isaacs, W. B. Regional loss of imprinting of the insulin-like growth factor II gene occurs in human prostate tissues. Clin Cancer Res, 1: 1471–1478, 1995.

    PubMed  CAS  Google Scholar 

  15. Steenman, M. J., Rainier, S., Dobry, C. J., Grundy, P., Horon, I. L., and Feinberg, A. P. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms’ tumour. Nat Genet, 7: 433–439, 1994.

    Article  PubMed  CAS  Google Scholar 

  16. Cui, H., Onyango, P., Brandenburg, S., Wu, Y., Hsieh, C. L., and Feinberg, A. P. Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res, 62: 6442–6446, 2002.

    PubMed  CAS  Google Scholar 

  17. Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet , 3: 662–673, 2002.

    Article  PubMed  CAS  Google Scholar 

  18. Barr, M. L. and Bertram, E. G. A morphological distinction between neurons of the male and female. Nature, 163: 676–677, 1949.

    Article  PubMed  CAS  Google Scholar 

  19. Ohno, S., Kaplan, W. D., and Kinosita, R. Formation of the sex chromatin by a single X-chromosome in liver cells of Rattus norvegicus. Exp Cell Res, 18: 415–418, 1959.

    Article  PubMed  CAS  Google Scholar 

  20. Lyon, M. F. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature, 190: 372–373, 1961.

    Article  PubMed  CAS  Google Scholar 

  21. Bender, J. Cytosine methylation of repeated sequences in eukaryotes: the role of DNA pairing. Trends Biochem Sci, 23: 252–256, 1998.

    Article  PubMed  CAS  Google Scholar 

  22. Ushijima, T., Morimura, K., Hosoya, Y., Okonogi, H., Tatematsu, M., Sugimura, T., and Nagao, M. Establishment of methylation-sensitive-representational difference analysis and isolation of hypo- and hypermethylated genomic fragments in mouse liver tumors. Proc Natl Acad Sci USA, 94: 2284–2289, 1997.

    Article  PubMed  CAS  Google Scholar 

  23. Suzuki, K., Suzuki, I., Leodolter, A., Alonso, S., Horiuchi, S., Yamashita, K., and Perucho, M. Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell, 9: 199–207, 2006.

    Article  PubMed  CAS  Google Scholar 

  24. Rodriguez, J., Frigola, J., Vendrell, E., Risques, R. A., Fraga, M. F., Morales, C., Moreno, V., Esteller, M., Capella, G., Ribas, M., and Peinado, M. A. Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res, 66: 8462–9468, 2006.

    Article  PubMed  CAS  Google Scholar 

  25. Bird, A. P. CpG-rich islands and the function of DNA methylation. Nature, 321: 209–213, 1986.

    Article  PubMed  CAS  Google Scholar 

  26. Cross, S. H., Charlton, J. A., Nan, X., and Bird, A. P. Purification of CpG islands using a methylated DNA binding column. Nat Genet, 6: 236–244, 1994.

    Article  PubMed  CAS  Google Scholar 

  27. Song, F., Smith, J. F., Kimura, M. T., Morrow, A. D., Matsuyama, T., Nagase, H., and Held, W. A. Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression. Proc Natl Acad Sci USA, 102: 3336–3341, 2005.

    Article  PubMed  CAS  Google Scholar 

  28. Feinberg, A. P., Gehrke, C. W., Kuo, K. C., and Ehrlich, M. Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res, 48: 1159–1161,1988.

    Google Scholar 

  29. Goelz, S. E., Vogelstein, B., Hamilton, S. R., and Feinberg, A. P. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science, 228: 187–190, 1985.

    Article  PubMed  CAS  Google Scholar 

  30. Feinberg, A. P. and Vogelstein, B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature, 301: 89–92, 1983.

    Article  PubMed  CAS  Google Scholar 

  31. Feinberg, A. P. and Vogelstein, B. Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Commun, 111: 47–54, 1983.

    Article  PubMed  CAS  Google Scholar 

  32. Bedford, M. T. and van Helden, P. D. Hypomethylation of DNA in pathological conditions of the human prostate. Cancer Res, 47: 5274–5276, 1987.

    PubMed  CAS  Google Scholar 

  33. Gama-Sosa, M. A., Slagel, V. A., Trewyn, R. W., Oxenhandler, R., Kuo, K. C., Gehrke, C. W., and Ehrlich, M. The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res, 11: 6883–6894, 1983.

    Article  PubMed  CAS  Google Scholar 

  34. Feinberg, A. P. and Tycko, B. The history of cancer epigenetics. Nat Rev Cancer, 4: 143–153, 2004.

    Article  PubMed  CAS  Google Scholar 

  35. Cadieux, B., Ching, T. T., Vandenberg, S. R., and Costello, J. F. Genome-wide hypomethylation in human glioblastomas associated with specific copy number alteration, methylenetetrahydrofolate reductase allele status, and increased proliferation. Cancer Res, 66: 8469–8476, 2006.

    Article  PubMed  CAS  Google Scholar 

  36. Lee, W. H., Morton, R. A., Epstein, J. I., Brooks, J. D., Campbell, P. A., Bova, G. S., Hsieh, W. S., Isaacs, W. B., and Nelson, W. G. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci USA, 91: 11733–11737, 1994.

    Article  PubMed  CAS  Google Scholar 

  37. Esteller, M., Corn, P. G., Baylin, S. B., and Herman, J. G. A gene hypermethylation profile of human cancer. Cancer Res, 61: 3225–3229, 2001.

    PubMed  CAS  Google Scholar 

  38. Jones, P. A. and Laird, P. W. Cancer epigenetics comes of age. Nat Genet, 21: 163–167, 1999.

    Article  PubMed  CAS  Google Scholar 

  39. Ehrlich, M. DNA methylation in cancer: too much, but also too little. Oncogene, 21: 5400–5413, 2002.

    Article  PubMed  CAS  Google Scholar 

  40. Holst, C. R., Nuovo, G. J., Esteller, M., Chew, K., Baylin, S. B., Herman, J. G., and Tlsty, T. D. Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epithelia. Cancer Res, 63: 1596–1601, 2003.

    PubMed  CAS  Google Scholar 

  41. Myohanen, S. K., Baylin, S. B., and Herman, J. G. Hypermethylation can selectively silence individual p16ink4A alleles in neoplasia. Cancer Res, 58: 591–593, 1998.

    PubMed  CAS  Google Scholar 

  42. Lin, X. and Nelson, W. G. Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells. Cancer Res, 63: 498–504, 2003.

    PubMed  CAS  Google Scholar 

  43. David, G. L., Yegnasubramanian, S., Kumar, A., Marchi, V. L., de Marzo, A. M., Lin, X., and Nelson, W. G. MDR1 promoter hypermethylation in MCF-7 human breast cancer cells: changes in chromatin structure induced by treatment with 5-aza-cytidine. Cancer Biol Ther, 3: 540–548, 2004.

    PubMed  CAS  Google Scholar 

  44. Pradhan, S., Bacolla, A., Wells, R. D., and Roberts, R. J. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem, 274: 33002–33010, 1999.

    Article  PubMed  CAS  Google Scholar 

  45. Gowher, H. and Jeltsch, A. Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: the enzyme modifies DNA in a non-processive manner and also methylates non-CpG [correction of non-CpA] sites. J Mol Biol, 309: 1201–1208, 2001.

    Article  PubMed  CAS  Google Scholar 

  46. Okano, M., Xie, S., and Li, E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet, 19: 219–220, 1998.

    Article  PubMed  CAS  Google Scholar 

  47. Jeltsch, A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chembiochem, 3: 274–293, 2002.

    Article  PubMed  CAS  Google Scholar 

  48. Okano, M., Bell, D. W., Haber, D. A., and Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99: 247–257, 1999.

    Article  PubMed  CAS  Google Scholar 

  49. Rhee, I., Jair, K. W., Yen, R. W., Lengauer, C., Herman, J. G., Kinzler, K. W., Vogelstein, B., Baylin, S. B., and Schuebel, K. E. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature, 404: 1003–1007, 2000.

    Article  PubMed  CAS  Google Scholar 

  50. Rhee, I., Bachman, K. E., Park, B. H., Jair, K. W., Yen, R. W., Schuebel, K. E., Cui, H., Feinberg, A. P., Lengauer, C., Kinzler, K. W., Baylin, S. B., and Vogelstein, B. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature, 416: 552–556, 2002.

    Article  PubMed  CAS  Google Scholar 

  51. Graff, J. R., Herman, J. G., Myohanen, S., Baylin, S. B., and Vertino, P. M. Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation. J Biol Chem, 272: 22322–22329, 1997.

    Article  PubMed  CAS  Google Scholar 

  52. Vertino, P. M., Yen, R. W., Gao, J., and Baylin, S. B. de novo methylation of CpG island sequences in human fibroblasts overexpressing DNA (cytosine-5-)-methyltransferase. Mol Cell Biol, 16: 4555–4565, 1996.

    PubMed  CAS  Google Scholar 

  53. Feltus, F. A., Lee, E. K., Costello, J. F., Plass, C., and Vertino, P. M. Predicting aberrant CpG island methylation. Proc Natl Acad Sci USA, 100: 12253–12258, 2003.

    Article  PubMed  CAS  Google Scholar 

  54. Bakin, A. V. and Curran, T. Role of DNA 5-methylcytosine transferase in cell transformation by fos. Science, 283: 387–390, 1999.

    Article  PubMed  CAS  Google Scholar 

  55. Laird, P. W., Jackson-Grusby, L., Fazeli, A., Dickinson, S. L., Jung, W. E., Li, E., Weinberg, R. A., and Jaenisch, R. Suppression of intestinal neoplasia by DNA hypomethylation. Cell, 81: 197–205, 1995.

    Article  PubMed  CAS  Google Scholar 

  56. Eads, C. A., Nickel, A. E., and Laird, P. W. Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic mice. Cancer Res, 62: 1296–1299, 2002.

    PubMed  CAS  Google Scholar 

  57. Belinsky, S. A., Klinge, D. M., Stidley, C. A., Issa, J. P., Herman, J. G., March, T. H., and Baylin, S. B. Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res, 63: 7089–7093, 2003.

    PubMed  CAS  Google Scholar 

  58. Eden, A., Gaudet, F., Waghmare, A., and Jaenisch, R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science , 300: 455, 2003.

    Google Scholar 

  59. Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., Leonhardt, H., and Jaenisch, R. Induction of tumors in mice by genomic hypomethylation. Science, 300: 489–492, 2003.

    Article  PubMed  CAS  Google Scholar 

  60. McCabe, M. T., Davis, J. N., and Day, M. L. Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. Cancer Res, 65: 3624–3632, 2005.

    Article  PubMed  CAS  Google Scholar 

  61. Eads, C. A., Danenberg, K. D., Kawakami, K., Saltz, L. B., Danenberg, P. V., and Laird, P. W. CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. Cancer Res, 59: 2302–2306, 1999.

    PubMed  CAS  Google Scholar 

  62. Agoston, A. T., Argani, P., Yegnasubramanian, S., de Marzo, A. M., Ansari-Lari, M. A., Hicks, J. L., Davidson, N. E., and Nelson, W. G. Increased protein stability causes DNA methyltransferase 1 dysregulation in breast cancer. J Biol Chem, 280:18302–18310, 2005.

    Article  PubMed  CAS  Google Scholar 

  63. Lande-Diner, L. and Cedar, H. Silence of the genes—mechanisms of long-term repression. Nat Rev Genet, 6: 648–654, 2005.

    Article  PubMed  CAS  Google Scholar 

  64. Klose, R. J. and Bird, A. P. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci, 31: 89–97, 2006.

    Article  PubMed  CAS  Google Scholar 

  65. Roloff, T. C., Ropers, H. H., and Nuber, U. A. Comparative study of methyl-CpG-binding domain proteins. BMC Genomics, 4: 1, 2003.

    Google Scholar 

  66. Prokhortchouk, A., Hendrich, B., Jorgensen, H., Ruzov, A., Wilm, M., Georgiev, G., Bird, A., and Prokhortchouk, E. The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev, 15: 1613–1618, 2001.

    Article  PubMed  CAS  Google Scholar 

  67. Filion, G. J., Zhenilo, S., Salozhin, S., Yamada, D., Prokhortchouk, E., and Defossez, P. A. A family of human zinc finger proteins that bind methylated DNA and repress transcription. Mol Cell Biol, 26: 169–181, 2006.

    Article  PubMed  CAS  Google Scholar 

  68. Daniel, J. M., Spring, C. M., Crawford, H. C., Reynolds, A. B., and Baig, A. The p120(ctn)-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides. Nucleic Acids Res, 30: 2911–2919, 2002.

    Article  PubMed  CAS  Google Scholar 

  69. Bird, A. P. and Wolffe, A. P. Methylation-induced repression—belts, braces, and chromatin. Cell, 99: 451–454, 1999.

    Article  PubMed  CAS  Google Scholar 

  70. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J. R., Cole, P. A., and Casero, R. A. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 119: 941–953, 2004.

    Article  PubMed  CAS  Google Scholar 

  71. Klose, R. J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J., and Zhang, Y. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature, 442: 312–316, 2006.

    Article  PubMed  CAS  Google Scholar 

  72. Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J., and Zhang, Y. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell , 125: 483–495, 2006.

    Article  PubMed  CAS  Google Scholar 

  73. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M. E., Borchers, C. H., Tempst, P., and Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature, 439: 811–816, 2006.

    Article  PubMed  CAS  Google Scholar 

  74. Zhang, K. and Dent, S. Y. Histone modifying enzymes and cancer: going beyond histones. J Cell Biochem, 96: 1137–1148, 2005.

    Article  PubMed  CAS  Google Scholar 

  75. Jones, P. L., Veenstra, G. J., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., and Wolffe, A. P. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet, 19: 187–191, 1998.

    Article  PubMed  CAS  Google Scholar 

  76. Feng, Q. and Zhang, Y. The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes. Genes Dev, 15: 827–832, 2001.

    PubMed  CAS  Google Scholar 

  77. Sarraf, S. A. and Stancheva, I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell, 15: 595–605, 2004.

    Article  PubMed  CAS  Google Scholar 

  78. Li, H., Rauch, T., Chen, Z. X., Szabo, P. E., Riggs, A. D., and Pfeifer, G. P. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem, 281: 19489–19500, 2006.

    Article  PubMed  CAS  Google Scholar 

  79. Yoon, H. G., Chan, D. W., Reynolds, A. B., Qin, J., and Wong, J. N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol Cell, 12: 723–734, 2003.

    Article  PubMed  CAS  Google Scholar 

  80. Hendrich, B., Guy, J., Ramsahoye, B., Wilson, V. A., and Bird, A. Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev, 15: 710–723, 2001.

    Article  PubMed  CAS  Google Scholar 

  81. Bakker, J., Lin, X., and Nelson, W. G. Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells. J Biol Chem, 277: 22573–22580, 2002.

    Article  PubMed  CAS  Google Scholar 

  82. Li, E., Bestor, T. H., and Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell, 69: 915–926, 1992.

    Article  PubMed  CAS  Google Scholar 

  83. Guy, J., Hendrich, B., Holmes, M., Martin, J. E., and Bird, A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet, 27: 322–326, 2001.

    Article  PubMed  CAS  Google Scholar 

  84. Klose, R. J., Sarraf, S. A., Schmiedeberg, L., McDermott, S. M., Stancheva, I., and Bird, A. P. DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. Mol Cell, 19: 667–678, 2005.

    Article  PubMed  CAS  Google Scholar 

  85. Gibbons, R. J. Histone modifying and chromatin remodelling enzymes in cancer and dysplastic syndromes. Hum Mol Genet, 14 Spec No 1: R85–92, 2005.

    Google Scholar 

  86. Keshet, I., Schlesinger, Y., Farkash, S., Rand, E., Hecht, M., Segal, E., Pikarski, E., Young, R. A., Niveleau, A., Cedar, H., and Simon, I. Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet, 38: 149–153, 2006.

    Article  PubMed  CAS  Google Scholar 

  87. Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J. M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y., and Fuks, F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature, 439: 871–874, 2006.

    Article  PubMed  CAS  Google Scholar 

  88. Nelson, W. G., de Marzo, A. M., and Isaacs, W. B. Prostate cancer. N Engl J Med, 349: 366–381, 2003.

    Article  PubMed  CAS  Google Scholar 

  89. Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., Sun, X. W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., Lee, C., Montie, J. E., Shah, R. B., Pienta, K. J., Rubin, M. A., and Chinnaiyan, A. M. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science, 310: 644–648, 2005.

    Article  PubMed  CAS  Google Scholar 

  90. Lin, X., Tascilar, M., Lee, W. H., Vles, W. J., Lee, B. H., Veeraswamy, R., Asgari, K., Freije, D., van Rees, B., Gage, W. R., Bova, G. S., Isaacs, W. B., Brooks, J. D., DeWeese, T. L., de Marzo, A. M., and Nelson, W. G. GSTP1 CpG island hypermethylation is responsible for the absence of GSTP1 expression in human prostate cancer cells. Am J Pathol, 159: 1815–1826, 2001.

    PubMed  CAS  Google Scholar 

  91. Henderson, C. J., Smith, A. G., Ure, J., Brown, K., Bacon, E. J., and Wolf, C. R. Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases. Proc Natl Acad Sci USA, 95: 5275–5280, 1998.

    Article  PubMed  CAS  Google Scholar 

  92. Nelson, C. P., Kidd, L. C., Sauvageot, J., Isaacs, W. B., de Marzo, A. M., Groopman, J. D., Nelson, W. G., and Kensler, T. W. Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S-transferase P1. Cancer Res, 61: 103–109, 2001.

    PubMed  CAS  Google Scholar 

  93. Shirai, T., Sano, M., Tamano, S., Takahashi, S., Hirose, M., Futakuchi, M., Hasegawa, R., Imaida, K., Matsumoto, K., Wakabayashi, K., Sugimura, T., and Ito, N. The prostate: a target for carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) derived from cooked foods. Cancer Res, 57: 195–198, 1997.

    PubMed  CAS  Google Scholar 

  94. Stuart, G. R., Holcroft, J., de Boer, J. G., and Glickman, B. W. Prostate mutations in rats induced by the suspected human carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res, 60: 266–268, 2000.

    PubMed  CAS  Google Scholar 

  95. de Marzo, A. M., Marchi, V. L., Epstein, J. I., and Nelson, W. G. Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol, 155: 1985–1992, 1999.

    PubMed  Google Scholar 

  96. Parsons, J. K., Nelson, C. P., Gage, W. R., Nelson, W. G., Kensler, T. W., and de Marzo, A. M. GSTA1 expression in normal, preneoplastic, and neoplastic human prostate tissue. Prostate, 49: 30–37, 2001.

    Article  PubMed  CAS  Google Scholar 

  97. Zha, S., Gage, W. R., Sauvageot, J., Saria, E. A., Putzi, M. J., Ewing, C. M., Faith, D. A., Nelson, W. G., de Marzo, A. M., and Isaacs, W. B. Cyclooxygenase-2 is up-regulated in proliferative inflammatory atrophy of the prostate, but not in prostate carcinoma. Cancer Res, 61: 8617–8623, 2001.

    PubMed  CAS  Google Scholar 

  98. DeMarzo, A. M., Nelson, W. G., Isaacs, W. B., and Epstein, J. I. Pathological and molecular aspects of prostate cancer. Lancet, 361: 955–964, 2003.

    Article  PubMed  CAS  Google Scholar 

  99. Nakayama, M., Bennett, C. J., Hicks, J. L., Epstein, J. I., Platz, E. A., Nelson, W. G., and de Marzo, A. M. Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Am J Pathol , 163: 923–933, 2003.

    PubMed  CAS  Google Scholar 

  100. Brooks, J. D., Weinstein, M., Lin, X., Sun, Y., Pin, S. S., Bova, G. S., Epstein, J. I., Isaacs, W. B., and Nelson, W. G. CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev, 7: 531–536, 1998.

    PubMed  CAS  Google Scholar 

  101. DeWeese, T. L. and Nelson, W. G. Inadequate “caretaker” gene function and human cancer development. Methods Mol Biol, 222: 249–268, 2003.

    PubMed  CAS  Google Scholar 

  102. Hmadcha, A., Bedoya, F. J., Sobrino, F., and Pintado, E. Methylation-dependent gene silencing induced by interleukin 1beta via nitric oxide production. J Exp Med, 190: 1595–1604, 1999.

    Article  PubMed  CAS  Google Scholar 

  103. Bastian, P. J., Yegnasubramanian, S., Palapattu, G. S., Rogers, C. G., Lin, X., de Marzo, A. M., and Nelson, W. G. Molecular biomarker in prostate cancer: the role of CpG island hypermethylation. Eur Urol, 46: 698–708, 2004.

    Article  PubMed  CAS  Google Scholar 

  104. Yegnasubramanian, S., Kowalski, J., Gonzalgo, M. L., Zahurak, M., Piantadosi, S., Walsh, P. C., Bova, G. S., de Marzo, A. M., Isaacs, W. B., and Nelson, W. G. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res, 64: 1975–1986, 2004.

    Article  PubMed  CAS  Google Scholar 

  105. Santourlidis, S., Florl, A., Ackermann, R., Wirtz, H. C., and Schulz, W. A. High frequency of alterations in DNA methylation in adenocarcinoma of the prostate. Prostate, 39: 166–174, 1999.

    Article  PubMed  CAS  Google Scholar 

  106. Florl, A. R., Steinhoff, C., Muller, M., Seifert, H. H., Hader, C., Engers, R., Ackermann, R., and Schulz, W. A. Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation. Br J Cancer, 91: 985–994, 2004.

    PubMed  CAS  Google Scholar 

  107. Schulz, W. A., Elo, J. P., Florl, A. R., Pennanen, S., Santourlidis, S., Engers, R., Buchardt, M., Seifert, H. H., and Visakorpi, T. Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma. Genes Chromosomes Cancer, 35: 58–65, 2002.

    Article  PubMed  CAS  Google Scholar 

  108. Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G., Otte, A. P., Rubin, M. A., and Chinnaiyan, A. M. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature, 419: 624–629, 2002.

    Article  PubMed  CAS  Google Scholar 

  109. Chen, H., Toyooka, S., Gazdar, A. F., and Hsieh, J. T. Epigenetic regulation of a novel tumor suppressor gene (hDAB2IP) in prostate cancer cell lines. J Biol Chem, 278: 3121–3130, 2003.

    Article  PubMed  CAS  Google Scholar 

  110. Chen, H., Tu, S. W., and Hsieh, J. T. Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J Biol Chem, 280: 22437–22444, 2005.

    Article  PubMed  CAS  Google Scholar 

  111. Bracken, A. P., Pasini, D., Capra, M., Prosperini, E., Colli, E., and Helin, K. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J, 22: 5323–5335, 2003.

    Article  PubMed  CAS  Google Scholar 

  112. Soh, S., Kattan, M. W., Berkman, S., Wheeler, T. M., and Scardino, P. T. Has there been a recent shift in the pathological features and prognosis of patients treated with radical prostatectomy? J Urol, 157: 2212–2218, 1997.

    Article  PubMed  CAS  Google Scholar 

  113. Thompson, I. M., Pauler, D. K., Goodman, P. J., Tangen, C. M., Lucia, M. S., Parnes, H. L., Minasian, L. M., Ford, L. G., Lippman, S. M., Crawford, E. D., Crowley, J. J., and Coltman, C. A., Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med, 350: 2239–2246, 2004.

    Article  PubMed  CAS  Google Scholar 

  114. Thompson, I. M., Goodman, P. J., Tangen, C. M., Lucia, M. S., Miller, G. J., Ford, L. G., Lieber, M. M., Cespedes, R. D., Atkins, J. N., Lippman, S. M., Carlin, S. M., Ryan, A., Szczepanek, C. M., Crowley, J. J., and Coltman, C. A., Jr. The influence of finasteride on the development of prostate cancer. N Engl J Med, 349: 215–224, 2003.

    Article  PubMed  CAS  Google Scholar 

  115. Makhlouf, A. A., Krupski, T. L., Kunkle, D., and Theodorescu, D. The effect of sampling more cores on the predictive accuracy of pathological grade and tumour distribution in the prostate biopsy. BJU Int, 93: 271–274, 2004.

    Article  PubMed  CAS  Google Scholar 

  116. de la Taille, A., Antiphon, P., Salomon, L., Cherfan, M., Porcher, R., Hoznek, A., Saint, F., Vordos, D., Cicco, A., Yiou, R., Zafrani, E. S., Chopin, D., and Abbou, C. C. Prospective evaluation of a 21-sample needle biopsy procedure designed to improve the prostate cancer detection rate. Urology, 61: 1181–1186, 2003.

    Article  Google Scholar 

  117. Sakr, W. A., Grignon, D. J., Crissman, J. D., Heilbrun, L. K., Cassin, B. J., Pontes, J. J., and Haas, G. P. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20–69: an autopsy study of 249 cases. In Vivo, 8: 439–443, 1994.

    PubMed  CAS  Google Scholar 

  118. Albertsen, P. C. What is the value of screening for prostate cancer in the US? Nat Clin Pract Oncol, 2: 536–537, 2005.

    Article  PubMed  Google Scholar 

  119. Sidransky, D. Emerging molecular markers of cancer. Nat Rev Cancer, 2: 210–219, 2002.

    Article  PubMed  CAS  Google Scholar 

  120. Laird, P. W. The power and the promise of DNA methylation markers. Nat Rev Cancer, 3: 253–266, 2003.

    Article  PubMed  CAS  Google Scholar 

  121. Bastian, P. J., Palapattu, G. S., Lin, X., Yegnasubramanian, S., Mangold, L. A., Trock, B., Eisenberger, M. A., Partin, A. W., and Nelson, W. G. Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res, 11: 4037–4043, 2005.

    Article  PubMed  CAS  Google Scholar 

  122. Singer, J., Roberts-Ems, J., and Riggs, A. D. Methylation of mouse liver DNA studied by means of the restriction enzymes msp I and hpa II. Science, 203: 1019–1021, 1979.

    Article  PubMed  CAS  Google Scholar 

  123. Bird, A. P. and Southern, E. M. Use of restriction enzymes to study eukaryotic DNA methylation: I. The methylation pattern in ribosomal DNA from Xenopus laevis. J Mol Biol, 118: 27–47, 1978.

    Google Scholar 

  124. Pollack, Y., Stein, R., Razin, A., and Cedar, H. Methylation of foreign DNA sequences in eukaryotic cells. Proc Natl Acad Sci USA, 77: 6463–6467, 1980.

    Article  PubMed  CAS  Google Scholar 

  125. Singer-Sam, J., Grant, M., LeBon, J. M., Okuyama, K., Chapman, V., Monk, M., and Riggs, A. D. Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Mol Cell Biol, 10: 4987–4989, 1990.

    PubMed  CAS  Google Scholar 

  126. Singer-Sam, J., LeBon, J. M., Tanguay, R. L., and Riggs, A. D. A quantitative HpaII-PCR assay to measure methylation of DNA from a small number of cells. Nucleic Acids Res, 18: 687, 1990.

    Article  PubMed  CAS  Google Scholar 

  127. Hatada, I., Kato, A., Morita, S., Obata, Y., Nagaoka, K., Sakurada, A., Sato, M., Horii, A., Tsujimoto, A., and Matsubara, K. A microarray-based method for detecting methylated loci. J Hum Genet , 47: 448–451, 2002.

    Article  PubMed  CAS  Google Scholar 

  128. Nygren, A. O., Ameziane, N., Duarte, H. M., Vijzelaar, R. N., Waisfisz, Q., Hess, C. J., Schouten, J. P., and Errami, A. Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res, 33: e128, 2005.

    Article  PubMed  CAS  Google Scholar 

  129. Hu, M., Yao, J., Cai, L., Bachman, K. E., van den Brule, F., Velculescu, V., and Polyak, K. Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet, 37: 899–905, 2005.

    Article  PubMed  CAS  Google Scholar 

  130. Schumacher, A., Kapranov, P., Kaminsky, Z., Flanagan, J., Assadzadeh, A., Yau, P., Virtanen, C., Winegarden, N., Cheng, J., Gingeras, T., and Petronis, A. Microarray-based DNA methylation profiling: technology and applications. Nucleic Acids Res, 34: 528–542, 2006.

    Article  PubMed  CAS  Google Scholar 

  131. Lippman, Z., Gendrel, A. V., Colot, V., and Martienssen, R. Profiling DNA methylation patterns using genomic tiling microarrays. Nat Methods, 2: 219–224, 2005.

    Article  PubMed  CAS  Google Scholar 

  132. Wang, R. Y., Gehrke, C. W., and Ehrlich, M. Comparison of bisulfite modification of 5-methyldeoxycytidine and deoxycytidine residues. Nucleic Acids Res, 8: 4777–4790, 1980.

    Article  PubMed  CAS  Google Scholar 

  133. Clark, S. J., Harrison, J., Paul, C. L., and Frommer, M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res, 22: 2990–2997, 1994.

    Article  PubMed  CAS  Google Scholar 

  134. Frommer, M., McDonald, L. E., Millar, D. S., Collis, C. M., Watt, F., Grigg, G. W., Molloy, P. L., and Paul, C. L. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA, 89: 1827–1831, 1992.

    Article  PubMed  CAS  Google Scholar 

  135. Herman, J. G., Graff, J. R., Myohanen, S., Nelkin, B. D., and Baylin, S. B. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA, 93: 9821–9826, 1996.

    Article  PubMed  CAS  Google Scholar 

  136. Eads, C. A., Danenberg, K. D., Kawakami, K., Saltz, L. B., Blake, C., Shibata, D., Danenberg, P. V., and Laird, P. W. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res, 28: E32, 2000.

    Article  PubMed  CAS  Google Scholar 

  137. Cottrell, S. E., Distler, J., Goodman, N. S., Mooney, S. H., Kluth, A., Olek, A., Schwope, I., Tetzner, R., Ziebarth, H., and Berlin, K. A real-time PCR assay for DNA-methylation using methylation-specific blockers. Nucleic Acids Res, 32: e10, 2004.

    Article  PubMed  Google Scholar 

  138. Thomassin, H., Kress, C., and Grange, T. MethylQuant: a sensitive method for quantifying methylation of specific cytosines within the genome. Nucleic Acids Res, 32: e168, 2004.

    Article  PubMed  CAS  Google Scholar 

  139. Xiong, Z. and Laird, P. W. COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res, 25: 2532–2534, 1997.

    Article  PubMed  CAS  Google Scholar 

  140. Gonzalgo, M. L. and Jones, P. A. Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE). Nucleic Acids Res, 25: 2529–2531, 1997.

    Article  PubMed  CAS  Google Scholar 

  141. Uhlmann, K., Brinckmann, A., Toliat, M. R., Ritter, H., and Nurnberg, P. Evaluation of a potential epigenetic biomarker by quantitative methyl-single nucleotide polymorphism analysis. Electrophoresis, 23: 4072–4079, 2002.

    Article  PubMed  CAS  Google Scholar 

  142. Huang, T. H., Perry, M. R., and Laux, D. E. Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet, 8: 459–470, 1999.

    Article  PubMed  CAS  Google Scholar 

  143. Adorjan, P., Distler, J., Lipscher, E., Model, F., Muller, J., Pelet, C., Braun, A., Florl, A. R., Gutig, D., Grabs, G., Howe, A., Kursar, M., Lesche, R., Leu, E., Lewin, A., Maier, S., Muller, V., Otto, T., Scholz, C., Schulz, W. A., Seifert, H. H., Schwope, I., Ziebarth, H., Berlin, K., Piepenbrock, C., and Olek, A. Tumour class prediction and discovery by microarray-based DNA methylation analysis. Nucleic Acids Res, 30: e21, 2002.

    Article  PubMed  Google Scholar 

  144. Gitan, R. S., Shi, H., Chen, C. M., Yan, P. S., and Huang, T. H. Methylation-specific oligonucleotide microarray: a new potential for high-throughput methylation analysis. Genome Res, 12: 158–164, 2002.

    Article  PubMed  CAS  Google Scholar 

  145. Bibikova, M., Lin, Z., Zhou, L., Chudin, E., Garcia, E. W., Wu, B., Doucet, D., Thomas, N. J., Wang, Y., Vollmer, E., Goldmann, T., Seifart, C., Jiang, W., Barker, D. L., Chee, M. S., Floros, J., and Fan, J. B. High-throughput DNA methylation profiling using universal bead arrays. Genome Res, 16: 383–393, 2006.

    Article  PubMed  CAS  Google Scholar 

  146. Ehrich, M., Nelson, M. R., Stanssens, P., Zabeau, M., Liloglou, T., Xinarianos, G., Cantor, C. R., Field, J. K., and van den Boom, D. Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA, 102: 15785–15790, 2005.

    Article  PubMed  CAS  Google Scholar 

  147. Brock, G. J., Huang, T. H., Chen, C. M., and Johnson, K. J. A novel technique for the identification of CpG islands exhibiting altered methylation patterns (ICEAMP). Nucleic Acids Res, 29: E123, 2001.

    Article  PubMed  CAS  Google Scholar 

  148. Shiraishi, M., Chuu, Y. H., and Sekiya, T. Isolation of DNA fragments associated with methylated CpG islands in human adenocarcinomas of the lung using a methylated DNA binding column and denaturing gradient gel electrophoresis. Proc Natl Acad Sci USA, 96: 2913–2918, 1999.

    Article  PubMed  CAS  Google Scholar 

  149. Rauch, T. and Pfeifer, G. P. Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer. Lab Invest, 85: 1172–1180,2005.

    Google Scholar 

  150. Weber, M., Davies, J. J., Wittig, D., Oakeley, E. J., Haase, M., Lam, W. L., and Schubeler, D. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet, 37: 853–862, 2005.

    Article  PubMed  CAS  Google Scholar 

  151. Gebhard, C., Schwarzfischer, L., Pham, T. H., Andreesen, R., Mackensen, A., and Rehli, M. Rapid and sensitive detection of CpG-methylation using methyl-binding (MB)-PCR. Nucleic Acids Res, 34: e82, 2006.

    Google Scholar 

  152. Yegnasubramanian, S., Lin, X., Haffner, M. C., DeMarzo, A. M., and Nelson, W. G. Combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes (COMPARE-MS) for the rapid, sensitive and quantitative detection of DNA methylation. Nucleic Acids Res, 34: e19, 2006.

    Article  PubMed  CAS  Google Scholar 

  153. Rauch, T., Li, H., Wu, X., and Pfeifer, G. P. MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells. Cancer Res, 66: 7939–7947, 2006.

    Article  PubMed  CAS  Google Scholar 

  154. Gebhard, C., Schwarzfischer, L., Pham, T. H., Schilling, E., Klug, M., Andreesen, R., and Rehli, M. Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia. Cancer Res, 66: 6118–6128, 2006.

    Article  PubMed  CAS  Google Scholar 

  155. Zhang, X., Yazaki, J., Sundaresan, A., Cokus, S., Chan, S. W., Chen, H., Henderson, I. R., Shinn, P., Pellegrini, M., Jacobsen, S. E., and Ecker, J. R. Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell, 126(6): 1189–201, 2006.

    Article  PubMed  CAS  Google Scholar 

  156. Millar, D. S., Ow, K. K., Paul, C. L., Russell, P. J., Molloy, P. L., and Clark, S. J. Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer. Oncogene, 18: 1313–1324, 1999.

    Article  PubMed  CAS  Google Scholar 

  157. Millar, D. S., Paul, C. L., Molloy, P. L., and Clark, S. J. A distinct sequence (ATAAA)n separates methylated and unmethylated domains at the 5′-end of the GSTP1 CpG island. J Biol Chem, 275: 24893–24899, 2000.

    Article  PubMed  CAS  Google Scholar 

  158. Harden, S. V., Guo, Z., Epstein, J. I., and Sidransky, D. Quantitative GSTP1 methylation clearly distinguishes benign prostatic tissue and limited prostate adenocarcinoma. J Urol, 169: 1138–1142, 2003.

    Article  PubMed  CAS  Google Scholar 

  159. Gonzalgo, M. L., Pavlovich, C. P., Lee, S. M., and Nelson, W. G. Prostate cancer detection by GSTP1 methylation analysis of postbiopsy urine specimens. Clin Cancer Res, 9: 2673–2677, 2003.

    PubMed  CAS  Google Scholar 

  160. Gonzalgo, M. L., Nakayama, M., Lee, S. M., de Marzo, A. M., and Nelson, W. G. Detection of GSTP1 methylation in prostatic secretions using combinatorial MSP analysis. Urology, 63(2): 414–8, 2004.

    Google Scholar 

  161. Jeronimo, C., Henrique, R., Hoque, M. O., Ribeiro, F. R., Oliveira, J., Fonseca, D., Teixeira, M. R., Lopes, C., and Sidransky, D. Quantitative RARbeta2 hypermethylation: a promising prostate cancer marker. Clin Cancer Res, 10: 4010–4014, 2004.

    Article  PubMed  CAS  Google Scholar 

  162. Liu, L., Yoon, J. H., Dammann, R., and Pfeifer, G. P. Frequent hypermethylation of the RASSF1A gene in prostate cancer. Oncogene, 21: 6835–6840, 2002.

    Article  PubMed  CAS  Google Scholar 

  163. Zhang, J., Liu, L., and Pfeifer, G. P. Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene. Oncogene, 23: 2241–2249, 2004.

    Article  PubMed  CAS  Google Scholar 

  164. Zhu, X., Leav, I., Leung, Y. K., Wu, M., Liu, Q., Gao, Y., McNeal, J. E., and Ho, S. M. Dynamic regulation of estrogen receptor-beta expression by DNA methylation during prostate cancer development and metastasis. Am J Pathol, 164: 2003–2012, 2004.

    PubMed  CAS  Google Scholar 

  165. Nelson, J. B., Chan-Tack, K., Hedican, S. P., Magnuson, S. R., Opgenorth, T. J., Bova, G. S., and Simons, J. W. Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. Cancer Res, 56: 663–668, 1996.

    PubMed  CAS  Google Scholar 

  166. Nelson, J. B., Hedican, S. P., George, D. J., Reddi, A. H., Piantadosi, S., Eisenberger, M. A., and Simons, J. W. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med, 1: 944–949, 1995.

    Article  PubMed  CAS  Google Scholar 

  167. Nelson, J. B., Lee, W. H., Nguyen, S. H., Jarrard, D. F., Brooks, J. D., Magnuson, S. R., Opgenorth, T. J., Nelson, W. G., and Bova, G. S. Methylation of the 5′ CpG island of the endothelin B receptor gene is common in human prostate cancer. Cancer Res, 57: 35–37, 1997.

    PubMed  CAS  Google Scholar 

  168. Nelson, J., Bagnato, A., Battistini, B., and Nisen, P. The endothelin axis: emerging role in cancer. Nat Rev Cancer, 3: 110–116, 2003.

    Article  PubMed  CAS  Google Scholar 

  169. Guise, T. A., Yin, J. J., and Mohammad, K. S. Role of endothelin-1 in osteoblastic bone metastases. Cancer, 97: 779–784, 2003.

    Article  PubMed  Google Scholar 

  170. Yin, J. J., Mohammad, K. S., Kakonen, S. M., Harris, S., Wu-Wong, J. R., Wessale, J. L., Padley, R. J., Garrett, I. R., Chirgwin, J. M., and Guise, T. A. A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA, 100: 10954–10959, 2003.

    Article  PubMed  CAS  Google Scholar 

  171. Carducci, M. A., Nelson, J. B., Bowling, M. K., Rogers, T., Eisenberger, M. A., Sinibaldi, V., Donehower, R., Leahy, T. L., Carr, R. A., Isaacson, J. D., Janus, T. J., Andre, A., Hosmane, B. S., and Padley, R. J. Atrasentan, an endothelin-receptor antagonist for refractoryadenocarcinomas: safety and pharmacokinetics. J Clin Oncol, 20: 2171–2180, 2002.

    Article  PubMed  CAS  Google Scholar 

  172. Carducci, M. A., Padley, R. J., Breul, J., Vogelzang, N. J., Zonnenberg, B. A., Daliani, D. D., Schulman, C. C., Nabulsi, A. A., Humerickhouse, R. A., Weinberg, M. A., Schmitt, J. L., and Nelson, J. B. Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. J Clin Oncol, 21: 679–689, 2003.

    Article  PubMed  CAS  Google Scholar 

  173. Kaminskas, E., Farrell, A., Abraham, S., Baird, A., Hsieh, L. S., Lee, S. L., Leighton, J. K., Patel, H., Rahman, A., Sridhara, R., Wang, Y. C., and Pazdur, R. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res, 11: 3604–3608, 2005.

    Article  PubMed  CAS  Google Scholar 

  174. Jones, P. A. and Taylor, S. M. Cellular differentiation, cytidine analogs and DNA methylation. Cell, 20: 85–93, 1980.

    Article  PubMed  CAS  Google Scholar 

  175. Cheng, J. C., Matsen, C. B., Gonzales, F. A., Ye, W., Greer, S., Marquez, V. E., Jones, P. A., and Selker, E. U. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst, 95: 399–409, 2003.

    Article  PubMed  CAS  Google Scholar 

  176. Lin, X., Asgari, K., Putzi, M. J., Gage, W. R., Yu, X., Cornblatt, B. S., Kumar, A., Piantadosi, S., DeWeese, T. L., de Marzo, A. M., and Nelson, W. G. Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide. Cancer Res, 61: 8611–8616, 2001.

    PubMed  CAS  Google Scholar 

  177. Segura-Pacheco, B., Trejo-Becerril, C., Perez-Cardenas, E., Taja-Chayeb, L., Mariscal, I., Chavez, A., Acuna, C., Salazar, A. M., Lizano, M., and Duenas-Gonzalez, A. Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin Cancer Res, 9: 1596–1603,2003.

    Google Scholar 

  178. Santini, V., Kantarjian, H. M., and Issa, J. P. Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann Intern Med, 134: 573–586, 2001.

    PubMed  CAS  Google Scholar 

  179. Juttermann, R., Li, E., and Jaenisch, R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci USA, 91: 11797–11801, 1994.

    Article  PubMed  CAS  Google Scholar 

  180. Yang, A. S., Doshi, K. D., Choi, S. W., Mason, J. B., Mannari, R. K., Gharybian, V., Luna, R., Rashid, A., Shen, L., Estecio, M. R., Kantarjian, H. M., Garcia-Manero, G., and Issa, J. P. DNA methylation changes after 5-aza-2′-deoxycytidine therapy in patients with leukemia. Cancer Res, 66: 5495–5503, 2006.

    Article  PubMed  CAS  Google Scholar 

  181. Thibault, A., Figg, W. D., Bergan, R. C., Lush, R. M., Myers, C. E., Tompkins, A., Reed, E., and Samid, D. A phase II study of 5-aza-2′deoxycytidine (decitabine) in hormone independent metastatic (D2) prostate cancer. Tumori, 84: 87–89, 1998.

    PubMed  CAS  Google Scholar 

  182. McCabe, M. T., Low, J. A., Daignault, S., Imperiale, M. J., Wojno, K. J., and Day, M. L. Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res, 66: 385–392, 2006.

    Article  PubMed  CAS  Google Scholar 

  183. Jackson-Grusby, L., Laird, P. W., Magge, S. N., Moeller, B. J., and Jaenisch, R. Mutagenicity of 5-aza-2′-deoxycytidine is mediated by the mammalian DNA methyltransferase. Proc Natl Acad Sci USA, 94: 4681–4685, 1997.

    Article  PubMed  CAS  Google Scholar 

  184. Scheinbart, L. S., Johnson, M. A., Gross, L. A., Edelstein, S. R., and Richardson, B. C. Procainamide inhibits DNA methyltransferase in a human T cell line. J Rheumatol, 18: 530–534, 1991.

    PubMed  CAS  Google Scholar 

  185. Cornacchia, E., Golbus, J., Maybaum, J., Strahler, J., Hanash, S., and Richardson, B. Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol, 140: 2197–2200, 1988.

    PubMed  CAS  Google Scholar 

  186. Lee, B. H., Yegnasubramanian, S., Lin, X., and Nelson, W. G. Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem, 280: 40749–40756, 2005.

    Article  PubMed  CAS  Google Scholar 

  187. Quddus, J., Johnson, K. J., Gavalchin, J., Amento, E. P., Chrisp, C. E., Yung, R. L., and Richardson, B. C. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest, 92: 38–53, 1993.

    Article  PubMed  CAS  Google Scholar 

  188. Kelly, W. K., Richon, V. M., O’Connor, O., Curley, T., MacGregor-Curtelli, B., Tong, W., Klang, M., Schwartz, L., Richardson, S., Rosa, E., Drobnjak, M., Cordon-Cordo, C., Chiao, J. H., Rifkind, R., Marks, P. A., and Scher, H. Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin Cancer Res, 9: 3578–3588, 2003.

    PubMed  CAS  Google Scholar 

  189. Carducci, M. A., Gilbert, J., Bowling, M. K., Noe, D., Eisenberger, M. A., Sinibaldi, V., Zabelina, Y., Chen, T. L., Grochow, L. B., and Donehower, R. C. A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-h infusion schedule. Clin Cancer Res, 7: 3047–3055, 2001.

    PubMed  CAS  Google Scholar 

  190. Carducci, M. A., Nelson, J. B., Chan-Tack, K. M., Ayyagari, S. R., Sweatt, W. H., Campbell, P. A., Nelson, W. G., and Simons, J. W. Phenylbutyrate induces apoptosis in human prostate cancer and is more potent than phenylacetate. Clin Cancer Res, 2: 379–387, 1996.

    PubMed  CAS  Google Scholar 

  191. Gilbert, J., Baker, S. D., Bowling, M. K., Grochow, L., Figg, W. D., Zabelina, Y., Donehower, R. C., and Carducci, M. A. A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin Cancer Res, 7: 2292–2300, 2001.

    PubMed  CAS  Google Scholar 

  192. Rokhlin, O. W., Glover, R. B., Guseva, N. V., Taghiyev, A. F., Kohlgraf, K. G., and Cohen, M. B. Mechanisms of cell death induced by histone deacetylase inhibitors in androgen receptor-positive prostate cancer cells. Mol Cancer Res, 4: 113–123, 2006.

    Article  PubMed  CAS  Google Scholar 

  193. Qian, D. Z., Kato, Y., Shabbeer, S., Wei, Y., Verheul, H. M., Salumbides, B., Sanni, T., Atadja, P., and Pili, R. Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res, 12: 634–642, 2006.

    Article  PubMed  CAS  Google Scholar 

  194. Camphausen, K., Scott, T., Sproull, M., and Tofilon, P. J. Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation. Clin Cancer Res, 10: 6066–6071, 2004.

    Article  PubMed  CAS  Google Scholar 

  195. Fronsdal, K. and Saatcioglu, F. Histone deacetylase inhibitors differentially mediate apoptosis in prostate cancer cells. Prostate, 62: 299–306, 2005.

    Article  PubMed  CAS  Google Scholar 

  196. Qian, D. Z., Wang, X., Kachhap, S. K., Kato, Y., Wei, Y., Zhang, L., Atadja, P., and Pili, R. The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res, 64: 6626–6634, 2004.

    Article  PubMed  CAS  Google Scholar 

  197. Camphausen, K., Burgan, W., Cerra, M., Oswald, K. A., Trepel, J. B., Lee, M. J., and Tofilon, P. J. Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275. Cancer Res, 64: 316–321, 2004.

    Article  PubMed  CAS  Google Scholar 

  198. Rashid, S. F., Moore, J. S., Walker, E., Driver, P. M., Engel, J., Edwards, C. E., Brown, G., Uskokovic, M. R., and Campbell, M. J. Synergistic growth inhibition of prostate cancer cells by 1 alpha,25 Dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with either sodium butyrate or trichostatin A. Oncogene, 20: 1860–1872, 2001.

    Article  PubMed  CAS  Google Scholar 

  199. Butler, L. M., Webb, Y., Agus, D. B., Higgins, B., Tolentino, T. R., Kutko, M. C., LaQuaglia, M. P., Drobnjak, M., Cordon-Cardo, C., Scher, H. I., Breslow, R., Richon, V. M., Rifkind, R. A., and Marks, P. A. Inhibition of transformed cell growth and induction of cellular differentiation by pyroxamide, an inhibitor of histone deacetylase. Clin Cancer Res, 7: 962–970, 2001.

    PubMed  CAS  Google Scholar 

  200. Butler, L. M., Agus, D. B., Scher, H. I., Higgins, B., Rose, A., Cordon-Cardo, C., Thaler, H. T., Rifkind, R. A., Marks, P. A., and Richon, V. M. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res, 60: 5165–5170, 2000.

    PubMed  CAS  Google Scholar 

  201. Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G., and Baylin, S. B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet, 21: 103–107, 1999.

    Article  PubMed  CAS  Google Scholar 

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Yegnasubramanian, S., Nelson, W.G. (2008). Epigenetic Gene Silencing in Prostate Cancer. In: Pestell, R.G., Nevalainen, M.T., Milken, M. (eds) Prostate Cancer. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-60327-079-3_2

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