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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。
G protein-coupled receptor-30 (G protein-coupled receptor 30, GPR30) is a novel membrane-associated estrogen receptor (ER). Tamoxifen (TAM) and its metabolite 4-hydroxamoxifen (OHT) are GPR30 agonists. The activation of GPR30 may lead to the development of TAM resistance. GPR30 may transactivate epidermal growth factor receptor (EGFR) and mediate the effect of E2 proliferation. It may have a synergistic effect with ERα and participate in the proliferation of breast cancer cells. Invasion and transfer behavior. As a competitive inhibitor of ERα (+), TAM occupies an important position in endocrine therapy of breast cancer, but the long-term use of TAM resistance limits its clinical application. EGFR and ER-related signaling pathways play an important role in TAM resistance mechanisms. Studies have shown that GPR30 can reverse TAM into a pro-growth stimulator and promote tumor growth. In this paper, the mechanism of GPR30 and TAM resistance mechanism as a starting point to explore GPR30 TAM resistance in the role.