TY - JOUR A1 - Weissenborn, Christine A1 - Ignatov, Tanja A1 - Ochel, Hans-Joachim A1 - Costa, Serban Dan A1 - Zenclussen, Ana Claudia A1 - Ignatova, Zoya A1 - Ignatov, Atanas T1 - GPER functions as a tumor suppressor in triple-negative breast cancer cells JF - Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft N2 - We investigated the role of GPER as a potential tumor suppressor in triple-negative breast cancer cells MDA-MB-231 and MDA-MB-468 using cell cycle analysis and apoptosis assay. The constitutive activity of GPER was investigated. GPER-specific activation with G-1 agonist inhibited breast cancer cell growth in concentration-dependent manner via induction of the cell cycle arrest in G2/M phase, enhanced phosphorylation of histone H3 and caspase-3-mediated apoptosis. Analysis of the methylation status of the GPER promoter in the triple-negative breast cancer cells and in tissues derived from breast cancer patients revealed that GPER amount is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Furthermore, GPER expression was induced by stress factors, such as radiation, and GPER amount inversely correlated with the p53 expression level. Overall, our results establish the protective role in breast cancer tumorigenesis, and the cell surface expression of GPER makes it an excellent potential therapeutic target for triple-negative breast cancer. KW - GPER KW - GPR30 KW - Breast cancer KW - Tumor suppression KW - TNBC Y1 - 2014 U6 - https://doi.org/10.1007/s00432-014-1620-8 SN - 0171-5216 SN - 1432-1335 VL - 140 IS - 5 SP - 713 EP - 723 PB - Springer CY - New York ER -