GPR30 promotes MCF-7 breast cancer cell migration and invasion by activating HER2-ERK1/2 signaling pathway / 重庆医学

ABSTRACT

Objective To study the molecular mechanism and biological significance of GPR30 activating HER2 in MCF-7 breast cancer cells with low expresses HER2.Methods Western blot was adopted to examine the phosphorylation of HER2 and the downstream signaling molecular ERK1/2 after 17-β-estradiol(E2),4-OHT(the active metabolite of tamoxifen) or G-1 (the GPR30 agonist) treatment in MCF-7 cells.After different inhibitors such as G-15 (the GPR30 antagonist),AG1478(EGFR tyrosine inhibitor),AG825 (HER2 tyrosine inhibitor),PP2 (Src family kinase inhibitor)or GM6001 (MMP inhibitor) pretreated for 2 h,the phosphorylation of HER2 and ERK1/2 were further analyzed.Finally,the altered migration and invasive capability of MCF-7 cells were detected by Transwell method.Results HER2 and ERK1/2 were activated in MCF-7 cells after E2,4-OHT or G-1 treatment and these changes could be inhibited by G-15,AG1478,AG825,PP2 or GM6001 pretreatment.The enhancement of G-1-induced migration and invasion ability in MCF-7 cells could also be inhibited by those inhibitors too.Conclusion GPR30 promotes the migration and invasion of MCF-7 cells through activating HER2-ERK1/2 signal transduction pathway.