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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

Je Kang Hoon    (Natural Products Research Institute, Seoul National University   ); Kim Ki Nam    (Natural Products Research Institute, Seoul National University   ); Nam Kung Woo    (Natural Products Research Institute, Seoul National University   ); Cho Myung Haing    (NIAST, RDA and College of Veterinary Medicine, Seoul National University   ); Mar Woong Chon    (Natural Products Research Institute, Seoul National University, College of Pharmacy, Seoul National University  );
  • 초록

    Endosulfan is one of the organochlorine pesticides, which are well-known endocrine disruptors (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 plasm ids 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.


  • 참고문헌 (32)

    1. Andersen, H. R., Vinggaard, A. M., Rasmussen, T. H., Gjermandsen, I. M., and Bonefeld-Jorgensen, E. C., Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicol. Appl. Pharmacol., 179, 1-12 (2002) 
    2. 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) 
    3. 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) 
    4. 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) 
    5. 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) 
    6. 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) 
    7. 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) 
    8. Wade, M. G., Desaulniers, D., Leingartner, K., and Foster, W. G., Interactions between endosulfan and dieldrin on estrogen-mediated processes in vitro and in vivo. Reprod. Toxicol., 11, 791-798 (1997) 
    9. 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) 
    10. 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) 
    11. 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) 
    12. 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) 
    13. 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) 
    14. 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) 
    15. 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) 
    16. 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) 
    17. 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) 
    18. 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) 
    19. Harley, C. B., Telomerase and telomerase in aging and cancer. Curr. Opin. Genet. Dev., 5, 249-255 (1995) 
    20. 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, 1alpha-hydroxyvitamin D5. J. Natl. Cancer Inst. 89, 212-218 (1997) 
    21. 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) 
    22. 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) 
    23. 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) 
    24. 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) 
    25. Madina, D., The preneoplastic phenotype in murine mammary tumorigenesis. J. Mammary Gland Biol. Neoplasia, 5, 393- 407 (2000) 
    26. 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) 
    27. 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) 
    28. 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) 
    29. Hodges, L. C., Bergerso, J. S., and Walker, C. L., Estrogenic effects of organochloride pesticides on uterine leiomyoma cells in vitro. Toxicol. Sci., 54, 355-364 (2000) 
    30. 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) 
    31. 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) 
    32. Sutton, G., Hormonal aspects of endometrial cancer. Curr. Opin. Obstet. Gynecol., 2, 69-73 (1990) 

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