title: TERT mRNA expression is up-regulated in MCF-7 cells and a mouse mammary organ culture (MMOC) system by endosulfan treatment.
abstract: 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 up-regulation 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.
authors.affiliation: Natural Products Research Institute, Seoul National University, Seoul 110-460, Korea.
authors.forename: Kang-Hoon
authors.initials: KH
authors.lastname: Je
authors.forename: Ki-Nam
authors.initials: KN
authors.lastname: Kim
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Woongchon
authors.initials: W
authors.lastname: Mar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins; D004726:Endosulfan / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010575:Pesticides / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D004967:Estrogens; D010575:Pesticides; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; D004726:Endosulfan