title: Progesterone-mediated regulation of catechol-O-methyl transferase expression in endometrial cancer cells.
abstract: The effects of estrogen and progesterone on the expression of estrogen-metabolizing enzymes such as catechol-O-methyl transferase (COMT) are not known. COMT converts genotoxic catecholestrogens to anticarcinogenic methoxyestrogens in the endometrium. The aim of this study is to investigate the effect of progesterone on COMT expression in well-differentiated endometrial cancer cells. The wild-type Ishikawa cell line as well as progesterone receptor A- or progesterone receptor B-transfected Ishikawa cells were used for in vitro studies. The regulation of COMT expression by progesterone was studied using Western blots, Hoechst dye DNA proliferation studies, and wild-type and/or site-directed mutagenesis of COMT promoter 1-luciferase reporter gene. Progesterone upregulated COMT protein expression in Ishikawa cells through progesterone receptor A isoform. COMT promoter activity was differentially regulated by the 3 half-site progesterone response elements in the COMT promoter. High doses of 2-ME2 inhibited Ishikawa cell proliferation. These data suggest that COMT expression is hormonally regulated in well-differentiated human endometrial cancer cells. COMT regulation and 2-ME2 production in the endometrium may affect endometrial carcinogenesis.
authors: Department of Obstetrics & Gynecology, University of Wisconsin, Madison, Wisconsin, USA.
authors: Sana M
authors: SM
authors: Salih
authors: Salama A
authors: SA
authors: Salama
authors: Mohammad
authors: M
authors: Jamaluddin
authors: Amin A
authors: AA
authors: Fadl
authors: Leen J
authors: LJ
authors: Blok
authors: Curt W
authors: CW
authors: Burger
authors: Manubai
authors: M
authors: Nagamani
authors: Ayman
authors: A
authors: Al-Hendy
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D011374:Progesterone / Q000378:metabolism*; D020033:Protein Isoforms; D011980:Receptors, Progesterone / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D020033:Protein Isoforms; D011980:Receptors, Progesterone; D011374:Progesterone; D002394:Catechol O-Methyltransferase