GPR30在乳腺癌内分泌治疗耐受中的作用研究

Advances the role of GPR30 in breast cancer endocrine therapy resistance

G蛋白偶联受体-30(G protein-coupled receptor 30,GPR30)是一种新型膜性结合性雌激素受体(estrogen receptor,ER)。他莫昔芬(tamoxifen,TAM)及其代谢产物4-羟他莫昔芬(4-hydroxtamoxifen,OHT)是GPR30激动剂。GPR30的激活可能导致TAM耐药性的发生,GPR30可反式激活表皮生长因子受体(epidermal growth factor receptor,EGFR),介导E2增殖效应,可能与ERα具有协同作用,参与乳腺癌细胞增殖、侵袭和转移等行为。TAM作为ERα(+)的竞争性抑制剂,在乳腺癌内分泌治疗中占据着重要的地位,但是长期应用TAM的耐药限制了其临床应用。EGFR及ER相关信号途径,在TAM耐药机制中扮演重要角色。研究证实GPR30可反转TAM变成促生长激动剂,促进肿瘤生长。本文从GPR30的作用机制和TAM的耐药性机制联系为出发点,探讨GPR30在TAM耐药性中的作用。

GPR30 is identified as a novel membrane-bound estrogen receptor （ER）. Tamoxifen and the metabolite 4-hydroxtamoxifen have been shown to act as GPR30 agonists. GPR30 activation may lead to tamoxifen resistance, and transactivate EGFR, promote E2-mediated cell proliferation and coordinate with ERα. It participates in breast cancer cell proliferation, invasion, transferance behavior. The ER（＋） antagonists tamoxifen occupys an important position in breast cancer endocrine therapy, but drug resistance limits its clinical applications. EGFR and ER signal transduction pathways play an important role in TAM resistance. This article focused on the role of GPR30 and TAM resistance mechanism, then discussed the role of GPR30 in TAM resistance.