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

被引：22

作者：

Levy, Nitzan ^{[2
,3
,4
,5
]}

Paruthiyil, Sreenivasan ^{[2
,3
,4
,5
]}

Zhao, Xiaoyue ^{[6
]}

Vivar, Omar I. ^{[2
,3
,4
,5
]}

Saunier, Elise F. ^{[6
]}

Griffin, Chandi ^{[2
,3
,4
,5
]}

Tagliaferri, Mary ^{[6
]}

Cohen, Isaac ^{[6
]}

Speed, Terence P. ^{[7
,8
]}

Leitman, Dale C. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

[2] Univ Calif San Francisco, Dept Obstet, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Gynecol, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Reprod Sci, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Ctr Reprod Sci Cellular & Mol Pharmacol, San Francisco, CA 94143 USA

[6] Bionovo Inc, Emeryville, CA USA

[7] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[8] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Bioinformat, Parkville, Vic 3050, Australia

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2010年 / 315卷 / 1-2期

关键词：

Estrogen receptor; Selective estrogen receptor modulator; Gene regulation; Tamoxifen; Microarray; BREAST-CANCER CELLS; ER-BETA; TRANSCRIPTIONAL ACTIVITY; TISSUE-SPECIFICITY; CYCLE ARREST; ALPHA; ACTIVATION; EXPRESSION; PROLIFERATION; RECRUITMENT;

D O I：

10.1016/j.mce.2009.08.030

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：201 / 207

页数：7

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