新型雌激素受体GPR30激活HER2-ERK1/2促进乳腺癌MCF-7细胞迁移和侵袭  

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

作　　者：阮姝琴 代晓燕[2] Ruan Shuqin Dai Xiaoyan(Department of Oncology and Hematology, Chongqing Municipal People＇s Hospital, Chongqing 400013, China Laboratory Room, Department of Oncology , Daping Hospital,Research Institute of Field Surgery, Third Military Medical University, Chongqing 400042, China)

机构地区：[1]重庆市人民医院肿瘤血液科,400013 [2]第三军医大学大坪医院野战外科研究所肿瘤科实验室,重庆400042

出　　处：《重庆医学》2017年第9期1168-1171,共4页Chongqing medicine

基　　金：2013年重庆市卫生局医学科研资助项目(2013-2-111);2013年重庆市渝中区科技计划项目(20130144)

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。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.

关 键 词：乳腺肿瘤 G蛋白耦联受体30 表皮生长因子受体2 细胞运动 侵袭 

分 类 号：R737.9[医药卫生—肿瘤]