Unliganded estrogen receptor-beta regulation of genes is inhibited by tamoxifen.
Mol Cell Endocrinol
; 315(1-2): 201-7, 2010 Feb 05.
Article
en En
| MEDLINE
| ID: mdl-19744542
ABSTRACT
Tamoxifen can stimulate the growth of some breast tumors and others can become resistant to tamoxifen. We previously showed that unliganded ERbeta inhibits ERalpha-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 ERbeta on gene regulation. Gene expression profiles demonstrated that unliganded ERbeta 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 ERbeta activates genes and how tamoxifen blocks this effect, we used doxycycline-inducible U2OS-ERbeta cells to produce unliganded ERbeta. Doxycycline produced a dose-dependent activation of the NKG2E, MSMB and TUB3A genes, which was abolished by tamoxifen. Unliganded ERbeta recruitment of SRC-2 to the NKG2E gene was blocked by tamoxifen. Our findings suggest that tamoxifen might exert a negative effect on ERbeta expressing tumors due to its antagonistic action on unliganded ERbeta.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Regulación Neoplásica de la Expresión Génica
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Receptor beta de Estrógeno
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Proliferación Celular
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Antagonistas de Estrógenos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos