GPER functions as a tumor suppressor in triple-negative breast cancer cells |
| |
Authors: | Christine Weißenborn Tanja Ignatov Hans-Joachim Ochel Serban Dan Costa Ana Claudia Zenclussen Zoya Ignatova Atanas Ignatov |
| |
Institution: | 1. Department of Obstetrics and Gynecology, University of Magdeburg, Gerhart-Hauptmann Str 35, Magdeburg, Germany 2. Department of Experimental Obstetrics and Gynaecology, University of Magdeburg, Magdeburg, Germany 3. Department of Radiotherapy, University of Magdeburg, Magdeburg, Germany 4. Department of Biochemistry and Biology, University of Potsdam, Potsdam, Germany
|
| |
Abstract: | Background The orphan, membrane-bound estrogen receptor (GPER) is expressed at high levels in a large fraction of breast cancer patients and its expression is favorable for patients’ survival. Methods 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. Results 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. Conclusions 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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|