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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.

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