中文摘要：

目的探讨G蛋白耦联受体30（GPR30）受体在低表达表皮生长因子受体2（HER2）的乳腺癌MCF-7细胞中激活HER2的分子机制和生物学意义。方法用Western blot的方法检测17-β-雌二醇（E2）、三苯氧胺（TAM）的活性代谢产物（4-OHT）或GPR30激动剂（G-1）作用于乳腺癌MCF-7细胞后HER2和下游信号分子ERK1/2磷酸化水平的变化。在MCF-7细胞被不同的抑制剂GPR30拮抗剂（G-15）、EGFR酪氨酸激酶抑制剂（AG1478）、HER2酪氨酸激酶抑制剂（AG825）、Src家族激酶抑制剂（PP2）或MMP抑制剂（GM6001）预处理2h后,再次检测HER2和ERK1/2的磷酸化水平变化。最后用Transwell方法检测G-1引起的MCF-7细胞迁移和侵袭能力的变化。结果 MCF-7细胞在用E2、4-OHT和G-1处理后,HER2和ERK1/2的磷酸化水平增加,该变化在用G-15、AG1478、AG825、PP2或GM6001预处理后受到抑制。而G-1引起的MCF-7细胞迁移和侵袭能力的增强也能被G-15、AG1478、AG825、PP2或GM6001抑制。结论GPR30通过激活HER2-ERK1/2信号转导途径可促进MCF-7细胞的迁移和侵袭。

英文摘要：

Objective To study the molecular mechanism and biological significance of GPR30 activating HER2in MCF-7breast cancer cells with low expresses HER2.Methods Western blot was adopted to examine the phosphorylation of HER2 and the downstream signaling molecular ERK1/2after 17-β-estradiol（E2）,4-OHT（the active metabolite of tamoxifen）or G-1（the GPR30agonist）treatment in MCF-7cells.After different inhibitors such as G-15（the GPR30antagonist）,AG1478（EGFR tyrosine inhibitor）,AG825（HER2tyrosine inhibitor）,PP2（Src family kinase inhibitor）or GM6001（MMP inhibitor）pretreated for 2h,the phosphorylation of HER2 and ERK1/2were further analyzed.Finally,the altered migration and invasive capability of MCF-7cells were detected by Transwell method.Results HER2 and ERK1/2were activated in MCF-7cells after E2,4-OHT or G-1treatment and these changes could be inhibited by G-15,AG1478,AG825,PP2 or GM6001pretreatment.The enhancement of G-1-induced migration and invasion ability in MCF-7cells could also be inhibited by those inhibitors too.Conclusion GPR30 promotes the migration and invasion of MCF-7cells through activating HER2-ERK1/2signal transduction pathway.