Unliganded estrogen receptor-beta regulation of genes is inhibited by tamoxifen

Levy, N; Paruthiyil, S; Zhao, XY; Vivar, OI; Saunier, EF; Griffin, C; Tagliaferri, M; Cohen, I; Speed, TP; Leitman, DC

Author(s): Levy, N; Paruthiyil, S; Zhao, XY; Vivar, OI; Saunier, EF; Griffin, C; Tagliaferri, M; Cohen, I; Speed, TP; Leitman, DC;
Details: Publication Year 2010-02-05,Volume 315,Issue #1-2,Page 201-207
Journal Title: MOLECULAR AND CELLULAR ENDOCRINOLOGY
Publication Type: Journal Article
Abstract: Tamoxifen can stimulate the growth of some breast tumors and others can become resistant-to tamoxifen. We previously showed that unliganded ER beta inhibits ER beta-mediated proliferation of MCF-7 cells. We investigated if tamoxifen might have a potential negative effect on some breast cancer cells by blocking the effects of unliganded ER beta on gene regulation. Gene expression profiles demonstrated that unliganded ER beta upregulated 196 genes in MCF-7 cells. Tamoxifen significantly inhibited 73 of these genes by greater than 30%, including several growth-inhibitory genes. To explore the mechanism whereby unliganded ER beta activates genes and how tamoxifen blocks this effect, we used doxycycline-inducible U20S-ER beta cells to produce unliganded ER beta. Doxycycline produced a dose-dependent activation of the NKG2E. MSMB and TUB3A genes, which was abolished by tamoxifen. Unliganded ER beta recruitment of SRC-2 to the NKG2E gene was blocked by tamoxifen. Our findings suggest that tamoxifen might exert a negative effect on ER beta expressing tumors due to its antagonistic action on unliganded ER beta. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
Publisher: ELSEVIER IRELAND LTD
Keywords: BREAST-CANCER CELLS; ER-BETA; TRANSCRIPTIONAL ACTIVITY; TISSUE-SPECIFICITY; CYCLE ARREST; ALPHA; ACTIVATION; EXPRESSION; PROLIFERATION; RECRUITMENT
Publisher's Version: https://doi.org/10.1016/j.mce.2009.08.030
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2010-02-05 12:00:00