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• W2103808181 startingPage "31" @default.
• W2103808181 abstract "Catechol-<i>O</i>-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson’s disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-β-estradiol (10⁻⁹–10⁻⁷ M) could decrease human 1.3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5′ to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-β-galactosidase plasmids into COS-7 cells, we showed that 17-β-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders." @default.
• W2103808181 created "2016-06-24" @default.
• W2103808181 creator A5035437162 @default.
• W2103808181 creator A5069072215 @default.
• W2103808181 creator A5073371884 @default.
• W2103808181 date "1999-07-01" @default.
• W2103808181 modified "2023-10-14" @default.
• W2103808181 title "Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-<i>O</i>-Methyltransferase Gene Transcription" @default.
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• W2103808181 doi "https://doi.org/10.1124/mol.56.1.31" @default.
• W2103808181 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10385681" @default.
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