PURPOSE: 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. We investigated the role of GPER as a potential tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells. METHODS: The effect of GPER agonist G-1 in cell culture was used to determine whether GPER inhibit cell growth. The methylation status of GPER promoter was investigated by methylation-specific PCR. RESULTS: GPER-specific agonist G-1 inhibited breast cancer cell proliferation in concentration-dependent manner via induction of the cell cycle arrest in M-phase, enhanced phosphorylation of histone 3 and cell apoptosis. Analysis of the methylation status of the GPER promoter in MCF-7 and SK-BR-3 cells revealed that GPER expression is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Overall, our results are consistent with our recent findings in triple-negative breast cancer cells, and the cell surface expression of GPER makes it an excellent potential therapeutic target for non-triple-negative breast cancer.
PURPOSE: The orphan, membrane-bound estrogen receptor (GPER) is expressed at high levels in a large fraction of breast cancerpatients, and its expression is favorable for patients' survival. We investigated the role of GPER as a potential tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells. METHODS: The effect of GPER agonist G-1 in cell culture was used to determine whether GPER inhibit cell growth. The methylation status of GPER promoter was investigated by methylation-specific PCR. RESULTS:GPER-specific agonist G-1 inhibited breast cancer cell proliferation in concentration-dependent manner via induction of the cell cycle arrest in M-phase, enhanced phosphorylation of histone 3 and cell apoptosis. Analysis of the methylation status of the GPER promoter in MCF-7 and SK-BR-3 cells revealed that GPER expression is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Overall, our results are consistent with our recent findings in triple-negative breast cancer cells, and the cell surface expression of GPER makes it an excellent potential therapeutic target for non-triple-negative breast cancer.
Authors: Megan K Dennis; Ritwik Burai; Chinnasamy Ramesh; Whitney K Petrie; Sara N Alcon; Tapan K Nayak; Cristian G Bologa; Andrei Leitao; Eugen Brailoiu; Elena Deliu; Nae J Dun; Larry A Sklar; Helen J Hathaway; Jeffrey B Arterburn; Tudor I Oprea; Eric R Prossnitz Journal: Nat Chem Biol Date: 2009-06 Impact factor: 15.040
Authors: A Chimento; I Casaburi; M Bartucci; M Patrizii; R Dattilo; P Avena; S Andò; V Pezzi; R Sirianni Journal: Cell Death Dis Date: 2013-08-01 Impact factor: 8.469
Authors: Xiangmin Lv; Chunbo He; Cong Huang; Guohua Hua; Zhengfeng Wang; Steven W Remmenga; Kerry J Rodabough; Adam R Karpf; Jixin Dong; John S Davis; Cheng Wang Journal: Mol Cancer Ther Date: 2017-03-03 Impact factor: 6.261