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Estrogen receptor beta exerts growth-inhibitory effects on human mammary epithelial cells.
Breast Cancer Res Treat. 2010 Apr; 120(3):557-65.BC

Abstract

Estrogen receptor beta (ERbeta) is widely expressed in mammary epithelium. ERbeta expression is reported to decline during carcinogenesis of the breast and other tissues. In this study, we examined the consequences of a loss of ERbeta expression in mammary epithelial cells. We knocked down ERbeta transcript levels in human mammary epithelial MCF-10A cells and in MCF-7 breast cancer cells by means of stable transfection with a specific shRNA plasmid. ERbeta knockdown resulted in a significant growth increase of both cell types in a ligand-independent manner. This effect was accompanied by elevated cyclin A2 expression in MCF-10A cells and by decreased expression of growth-inhibitory p21/WAF and epithelial cell marker cytokeratine 8 in both cell lines. Transfection of ERbeta shRNA did not alter the absent proliferative estrogen response of MCF-10A cells, but conferred sensitivity to selective estrogen receptor modulator tamoxifen to this cell line. In contrast, ERbeta knockdown diminished estrogen responsiveness of MCF-7 breast cancer cells and also weakened the effect of tamoxifen on this cell line. These ligand-dependent effects only observed in MCF-7 cells exhibiting a high ERalpha/beta ratio were accompanied by smaller estrogenic repression of p21/WAF expression, an impaired tamoxifen-triggered induction of this gene and by relative downregulation of ERalpha and cyclin A2 transcript levels. Our data suggest that ERbeta exerts antiproliferative effects both on MCF-10A and MCF-7 cells in a ligand- and ERalpha-independent manner by regulation of p21/WAF or cyclin A2 gene expression. Knockdown of ERbeta in both cell types was sufficient to significantly decrease transcript levels of epithelial cell marker cytokeratin 8. The results of this study support the hypothesis that ERbeta acts as a tumor suppressor in mammary epithelium.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, University of Regensburg, 93053, Regensburg, Germany. otreeck@caritasstjosef.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19434490

Citation

Treeck, Oliver, et al. "Estrogen Receptor Beta Exerts Growth-inhibitory Effects On Human Mammary Epithelial Cells." Breast Cancer Research and Treatment, vol. 120, no. 3, 2010, pp. 557-65.
Treeck O, Lattrich C, Springwald A, et al. Estrogen receptor beta exerts growth-inhibitory effects on human mammary epithelial cells. Breast Cancer Res Treat. 2010;120(3):557-65.
Treeck, O., Lattrich, C., Springwald, A., & Ortmann, O. (2010). Estrogen receptor beta exerts growth-inhibitory effects on human mammary epithelial cells. Breast Cancer Research and Treatment, 120(3), 557-65. https://doi.org/10.1007/s10549-009-0413-2
Treeck O, et al. Estrogen Receptor Beta Exerts Growth-inhibitory Effects On Human Mammary Epithelial Cells. Breast Cancer Res Treat. 2010;120(3):557-65. PubMed PMID: 19434490.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen receptor beta exerts growth-inhibitory effects on human mammary epithelial cells. AU - Treeck,Oliver, AU - Lattrich,Claus, AU - Springwald,Anette, AU - Ortmann,Olaf, Y1 - 2009/05/12/ PY - 2009/02/19/received PY - 2009/04/23/accepted PY - 2009/5/13/entrez PY - 2009/5/13/pubmed PY - 2010/6/18/medline SP - 557 EP - 65 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 120 IS - 3 N2 - Estrogen receptor beta (ERbeta) is widely expressed in mammary epithelium. ERbeta expression is reported to decline during carcinogenesis of the breast and other tissues. In this study, we examined the consequences of a loss of ERbeta expression in mammary epithelial cells. We knocked down ERbeta transcript levels in human mammary epithelial MCF-10A cells and in MCF-7 breast cancer cells by means of stable transfection with a specific shRNA plasmid. ERbeta knockdown resulted in a significant growth increase of both cell types in a ligand-independent manner. This effect was accompanied by elevated cyclin A2 expression in MCF-10A cells and by decreased expression of growth-inhibitory p21/WAF and epithelial cell marker cytokeratine 8 in both cell lines. Transfection of ERbeta shRNA did not alter the absent proliferative estrogen response of MCF-10A cells, but conferred sensitivity to selective estrogen receptor modulator tamoxifen to this cell line. In contrast, ERbeta knockdown diminished estrogen responsiveness of MCF-7 breast cancer cells and also weakened the effect of tamoxifen on this cell line. These ligand-dependent effects only observed in MCF-7 cells exhibiting a high ERalpha/beta ratio were accompanied by smaller estrogenic repression of p21/WAF expression, an impaired tamoxifen-triggered induction of this gene and by relative downregulation of ERalpha and cyclin A2 transcript levels. Our data suggest that ERbeta exerts antiproliferative effects both on MCF-10A and MCF-7 cells in a ligand- and ERalpha-independent manner by regulation of p21/WAF or cyclin A2 gene expression. Knockdown of ERbeta in both cell types was sufficient to significantly decrease transcript levels of epithelial cell marker cytokeratin 8. The results of this study support the hypothesis that ERbeta acts as a tumor suppressor in mammary epithelium. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/19434490/Estrogen_receptor_beta_exerts_growth_inhibitory_effects_on_human_mammary_epithelial_cells_ L2 - https://doi.org/10.1007/s10549-009-0413-2 DB - PRIME DP - Unbound Medicine ER -