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TERT mRNA expression is Up-regulated in MCF-7 cells and a mouse mammary organ culture (MMOC) system by endosulfan treatment

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Endosulfan is one of the organochlorine pesticides, which are well-known endocrine disrupters (EDs), and it acts as an estrogen agonist. Estrogen is a group of hormones that play an important role in mammary gland function and are implicated in mammary carcinogenesis. In the present study, we studied the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in mouse mammary gland development using a mouse mammary gland organ culture (MMOC) system. Although endosulfan-treated mammary glands did not form NLALs, more alveolar buds were formed in this group than in the negative control (vehicle-treated) group. In addition, telomerase reverse transcriptase (TERT) mRNA expression levels were increased in endosulfan-treated mammary glands in a dose-dependent manner. Telomerase can be activated by estrogen, therefore, we examined the effects of endosulfan on telomerase activity, and found that the telomerase activity in estrogen receptor-positive MCF-7 cells was up-regulated by endosulfan treatment. Moreover, this activation was accompanied by the upregulation of the TERT mRNA expression. Also, transient expression assays using CAT reporter plasmids containing various fragments of the TERT promoter showed that this imperfect palindromic estrogen-responsive element is almost certainly responsible for the transcriptional activation by endosulfan. These results may help elucidate the endocrine disrupting mechanism of endosulfan.

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References

  • Andersen, H. R., Vinggaard, A. M., Rasmussen, T. H., Gjermandsen, I. M., and Bonefeld-Jørgensen, E. C., Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activityin vitro. Toxicol. Appl. Pharmacol., 179, 1–12 (2002).

    Article  CAS  Google Scholar 

  • Barlow, J., Casey, T., Chiu, J-F., and Plaut, K., Estrogen affects development of alveolar structures in whole-organ culture of mouse mammary glands.Biochem. Biophys. Res. Commun., 232, 340–344 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Brien, T. P., Kallakury, B. V., Lowry, C. V., Ambros, R. A., Muraca, P. J., Malfetano, J. H., and Ross, J. S., Telomerase activity in benign endometrium and endometrial carcinoma.Cancer Res., 57, 2760–2764 (1997).

    PubMed  CAS  Google Scholar 

  • Coumoul, X., Diry, M., Robillot, C., and Barouki, R., Differential regulation of cytochrome P450 1A1 and 1B1 by a combination of dioxin and pesticides in the breast tumor cell line MCF-7.Cancer Res., 61, 3942–3948 (2001).

    PubMed  CAS  Google Scholar 

  • Feng, J., Funk, W. D., Wang, S. S., Weinrich, A. A. A., Chiu, C. P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., Le, S., West, M. D., Harley, C. B., Andrew, W. H., Greider, C. W., and Villeponteau, B., The RNA component of human telomerase.Science, 269, 1236–1241 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Gorman, C. M., Moffat, L. F., and Howard, B. H., Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.Mol. Cell Biol., 2, 1044–1051 (1982).

    PubMed  CAS  Google Scholar 

  • Greider, C. W. and Blackburn, E. H., A telomeric sequences in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.Nature, 337, 331–337 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Harrington, L., McPhail, T., Mar, V., Zhou, W., Oulton, R., Bass, M. B., Arruda, I., and Robinson, M. O., A mammalian telomerase-associated protein.Science, 275, 973–977 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Harley, C. B., Telomerase and telomerase in aging and cancer.Curr. Opin. Genet. Dev., 5, 249–255 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Hiyama, E., Gollahon, L., Kataoka, T., Kuroi, K., Yokoyama, T., Gazdar, A. F., Hiyama, K., Piatyszek, M. A., and Shay, J. W., Telomerase activity in human breast tumors.J. Natl. Cancer Inst., 88, 116–122 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Hodges, L. C., Bergerso, J.S., and Walker, C. L., Estrogenic effects of organochloride pesticides on uterine leiomyoma cellsIn vitro. Toxicol. Sci., 54, 355–364 (2000).

    Article  CAS  Google Scholar 

  • Holt, S. E., Shay, J. W., and Wright, W.E., Refining the telomere-telomerase hypothesis of aging and cancer.Nature Biotechnol., 14, 836–839 (1996).

    Article  CAS  Google Scholar 

  • Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. E., Ho, P. L., Coviello, G. M., Wright, W. E., Weinrich, S.L., and Shay, J.W., Specific association of human telomerase activity with immortal cells and cancer.Science, 266, 2011–2015 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Kolquist, K. A., Ellisen, L. W., Counter, C. M., Meyerson, M., Tan, L. K., Weinberg, R. A., Haber, D. A., and Gerald, W. L., Expression of TERT in early premalignant lesion and a subset of cells in normal tissues.Nature Genet., 19, 182–186 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Kyo, S., Takakura, M., Kohama, T., Sagawa, T., Yamashita, K., Okada, Y., Hiyama, E., and Inoue, M., Telomerase activity in human endometrium.Cancer Res., 57, 610–614 (1997).

    PubMed  CAS  Google Scholar 

  • Kyo, S., Takakura, M., Kanaya, T., Zhuo, W., Fujimoto, K., Nishio, Y., Orimo, A., and Inoue, M., Estrogen activates telomerase.Cancer Res., 59, 5917–5921 (1999).

    PubMed  CAS  Google Scholar 

  • Marcantonio, D., Chalifour, L. E., Alaoui-Jamali, M. A., Alpert, L., and Huynh, H. T., Cloning and characterzation of a novel gene that is regulated by estrogen and is associated with mammary gland carcinogenesis.Endocrinology, 142, 2409–2418 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Madina, D., The preneoplastic phenotype in murine mammary tumorigenesis.J. Mammary Gland Biol. Neoplasia, 5, 393–407 (2000).

    Article  Google Scholar 

  • Mehta, R. G., Hawthorne, M. E., and Steele, V. E., Induction and prevention of carcinogen-induced precancerous lesions in mouse mammary gland organ culture.Methods Cell Sci., 19, 19–24 (1997).

    Article  Google Scholar 

  • Mehta, R. G., Moriarty, R. M, Mehta, R. R, Penmasta, R., Lazzaro, G., Constantinou, A., and Guo, L., Prevention of preneoplastic mammary lesion development by a novel vitamin D analogue, lalpha-hydroxyvitamin D5.J. Natl. Cancer Inst. 89, 212–218 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Mehta, R. G., Williamson, E., Patel, M. K., and Koeffler, H.P., A ligand of peroxisome proliferator-activated receptor gamma, retinoids, and prevention of preneoplastic mammary lesions.J. Natl. Cancer Inst., 92, 418–423 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Muller, S. O. and Korach, K. S., Estrogen receptors and endocrine diseases:lessons from estrogen receptor knockout mice.Curr. Opin. Pharmacol., 1, 613–619 (2001).

    Article  Google Scholar 

  • Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., and Cech, T. R., Telomerase catalytic subunit homologs from fission yeast and human.Science, 277, 955–959 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Richert, M. M., Schwertfeger, K. L., Ryder, J. W., and Anderson, S. M., An atlas of mouse mammary gland development.J. Mammary Gland Biol. Neoplasia, 5, 227–241 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Soto, A. M., Chung, K. L., and Sonnenschein, C., The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells.Environ. Health Perspect., 102, 380–383 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Schmitt, E., Dekant, W., and Stopper, H., Assaying the estrogenicity of phytoestrogen in cells of different estrogen sensitive tissues.Toxicol, in Vitro, 15, 433–439 (2001).

    Article  CAS  Google Scholar 

  • Sutton, G., Hormonal aspects of endometrial cancer.Curr. Opin. Obstet. Gynecol., 2, 69–73 (1990).

    PubMed  CAS  Google Scholar 

  • Takakura, M., Kyo, S., Kanaya, T., Hirano, H., Takeda, J., Yutsudo, M., and Inoue, M., Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells.Cancer Res., 59, 551–557 (1999).

    PubMed  CAS  Google Scholar 

  • Varon, D., Jiang, C., Hedican, C., Dome, J. S., Umbricht, C. B., Carey, L. A., Thompson, H. J., and Sukumar, S., Telomerase activity in the normal and neoplastic rat mammary gland.Cancer Res., 57, 5605–5609 (1997).

    PubMed  CAS  Google Scholar 

  • Wade, M. G., Desaulniers, D., Leingartner, K., and Foster, W. G., Interactions between endosulfan and dieldrin on estrogen-mediated processesin vitro and in vivo.Reprod. Toxicol., 11, 791–798 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Weinrich, S. L., Pruzan, R., Ma, L., Ouellette, M., Tesmer, V. M., Holt, S. E., Bodnar, A. G., Lichtsteiner, S., Kim, N. W., Trager, J. B., Taylor, R. D., Carlos, R., Andrews, W. H., Wright, W. E., Shay, J. W., Harley, C. B., and Morin, G. B., Reconstitution of human telomerase with template RNA component hTERC and the catalytic protein subunit hTERT.Nat. Genet., 17, 498–502 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., and Dalla-Favera, R., Direct activation of TERT transcription by c-Myc.Nat. Genet., 21, 220–224 (1999).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Woongchon Mar.

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Je, KH., Kim, KN., Nam, KW. et al. TERT mRNA expression is Up-regulated in MCF-7 cells and a mouse mammary organ culture (MMOC) system by endosulfan treatment. Arch Pharm Res 28, 351–357 (2005). https://doi.org/10.1007/BF02977804

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