乳腺癌治疗新靶点GPER1研究进展

Advances on the new target GPER1 for therapy of breast cancer

目的:总结国内外对乳腺癌治疗新靶点G蛋白偶联雌激素受体(G protein-coupled estrogen receptor 1,GPER1/GPR30)的研究进展。方法:应用Medline、PubMed及CNKI期刊全文数据库检索系统,分别以"G蛋白偶联雌激素受体(GPER1/GPR30)"和"乳腺癌"、"G蛋白偶联雌激素受体(GPER1/GPR30)"和"乳腺癌内分泌治疗"为关键词,检索1997-2013年国内外的相关文献。纳入标准:1)GPER1参与的信号转导通路与乳腺癌;2)GPER1与乳腺癌抗雌激素治疗耐药性;3)GPER1与乳腺癌病理过程。依据纳入标准,纳入分析的参考文献为52篇。结果:GPER1是一种新型雌激素受体,它不但构建了慢速基因效应和快速非基因效应的交互通话,还通过表皮生长因子受体(epidermal growth factor receptor,EGFR)活化后参与蛋白激酶途径及通过第二信使cAMP、Ca2+途径介导快速非基因效应,发挥间接转录调控作用。GPER1介导了乳腺癌的发生发展,其激活可能促使乳腺癌细胞产生他莫昔芬(tamoxifen,TAM)耐药。结论:GPER1是新型的乳腺肿瘤标志。以GPER1及GPER1介导的信号通路为靶点的治疗将有望成为乳腺癌预防和治疗的新方案。

OBJECTIVE： To summarize the domestic and abroad acticles related to the research progresses about the relationship between G protein-coupled estrogen receptor-1 （GPER1, formerly called GPR30） and breast cancer. METH- ODS： ＂Breast cancer and G protein-coupled estrogen receptor-l＂ were searched as keywords by Medline, Pubmed and CNKI series fulltext database retrieval system from 1997-2013. Chioce criteria：GPER1 signaling in breast cancer;implication of GPER1 in the resistance to antiestrogen therapy;GPER1 and pathological processes of breast cancer. By extraction according to the chioce criteria,52 papers were selected and analyzed finally. RESULTS： The G protein-coupled estrogen receptor-1 has been recently involved the multifaceted transduction pathways which estrogens induce diverse biological responses and pathological processes, including breast cancer development and progression, and modulates both rapid non- genomic reaction and genomic transcriptional events of estrogen via transactivation of epidermal growth factor receptor （EGFR） and modulation of second messengers such as cyclic adenosine monophosphate （cAMP） and Ca2＋. In addition, GPER1 activation may lead to tamoxifen resistance. CONCLUSIONS： GPER1 has been recently considered as a valuable biological marker in breast carcinomas. According to the specific characteristics of GPER1 in breast cancer, targeting GPER1 or GPERl-dependent signaling may be a novel breast cancer therapy.