β-catenin is a positive regulator of estrogen receptor-α function in breast cancer cellsβ-catenin是一个积极监管机构的雌激素在乳腺癌细胞receptor-α函数.pdfVIP

Cancers 2011, 3, 2990-3001; doi:10.3390/cancers3032990 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Article β-Catenin Is a Positive Regulator of Estrogen Receptor-α Function in Breast Cancer Cells Nibedita Gupta, Fee Schmitt, Sina Grebhardt and Doris Mayer * Hormones and Signal Transduction Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; E-Mails: n.gupta@dkfz.de (N.G.); fee.schmitt@gmx.de (F.S.); s.grebhardt@dkfz.de (S.G.) * Author to whom correspondence should be addressed; E-Mail: d.mayer@dkfz.de; Tel.: +49-6221-423238; Fax: +49-6221-423237. Received: 9 June 2011; in revised form: 18 July 2011 / Accepted: 19 July 2011 / Published: 22 July 2011 Abstract: Estrogen receptor-alpha (ERα) is a key factor in the development of breast cancer in humans. The expression and activity of ERα is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between β-catenin and ERα in human breast cancer cells. Knockdown of β-catenin by RNAi resulted in significant reduction of ERα mRNA and/or protein levels in MCF-7, T-47D, and BT-474 breast cancer cells and in significant reduction of estradiol-induced expression of the ERα target genes pS2 and GREB1. In addition β-catenin silencing resulted in significant decrease of growth of MCF-7 cells both in the absence and presence of estradiol. β-catenin and ERα could not be co-immunoprecipitated by ERα antib