Progesterone-mediated regulation of catechol-O-methyl transferase expression in endometrial cancer cells

Sana M. Salih, Salama A. Salama, Mohammad Jamaluddin, Amin A. Fadl, Leen J. Blok, Curt W. Burger, Manubai Nagamani, Ayman Al-Hendy

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)210-220
Number of pages11
JournalReproductive Sciences
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • Catechol-o-methyl transferase
  • Endometrial cancer
  • Progesterone

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    Salih, S. M., Salama, S. A., Jamaluddin, M., Fadl, A. A., Blok, L. J., Burger, C. W., Nagamani, M., & Al-Hendy, A. (2008). Progesterone-mediated regulation of catechol-O-methyl transferase expression in endometrial cancer cells. Reproductive Sciences, 15(2), 210-220. https://doi.org/10.1177/1933719107310398