Estrogen ActivatesGPER-EGFR-ERK Pathway To Promote The Proliferation Of Human SKBR-3Breast Cancer Cell Line

Objective：To explore the effect of G protein coupling estrogenreceptor (G protein-coupled estrogen receptor, GPER) induced by estrogenon the proliferation in human SKBR-3breast cancer cell line.Methods：Calcium influx, cell growth ability and cell cycles werechecked by confocal laser scanning microscopy, CCK-8assay and flowcytometry in the presence of different drug treatment, respectively.Relative expression levels of extracellular signal regulating kinasephosphorylation (Phospho-extracellular regulated kinase, p-ERK) wasdetected by immune-blotting.Results: After treatment of17-β estradiol (E2) or GFER specificagonist (G1), inner cells calcium ion concentration was shifted quicklystarting from120seconds;cell proliferation was increased significantly,CCK-8assay relative cell number were（2.08±0.07）times and（2.0±0.04）times respectively compared to control group; proliferation index (PI)（43.12%±0.38%,42.43%±0.52%） in S phase and G2-M phase wasincreased dramatically compared to control group （29.19%±0.29%）(P<0.05); the protein level of p-ERK was much higher than that in control group (P<0.05). GFPE antagonist G15、EGFR antagonist AG1478andERK antagonist U0126can inhibit the changes which induced by E2orG1,but not the PI3K antagonist WM.Conclusion: Estrogen activates GPER-EGFR-ERK pathway topromote the proliferation of human SKBR-3breast cancer cellline.