The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells
The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells
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G蛋白偶联受体GPR30介导羟基他莫昔芬诱导的子宫内膜癌细胞增殖和侵袭作用
DOI：
10.1016/j.bbrc.2012.02.161
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发表时间：
2012-04-06
影响因子：
3.1
通讯作者：
He, Yin-Yan
中科院分区：
文献类型：
--
作者：
Du, Gui-Qiang;Zhou, Long;He, Yin-Yan
选择性ER调节剂他莫昔芬((1))是治疗激素依赖性乳腺肿瘤的最广泛使用的ER拮抗剂。然而，长期治疗会增加患子宫内膜癌的风险。本研究的目的是对G蛋白偶联受体30(GPR30)在促进子宫内膜癌的活动中的作用提供新的见解。在子宫内膜癌细胞系Ishikawa和KLE中，评价了的活性代谢产物4-羟基他莫昔芬、17β-雌二醇(E_2)和非甾体GPR30特异性激动剂G1促进细胞增殖和侵袭的潜力。当GPR30表达下调或MAPK信号通路阻断时，上述药物均可诱导细胞高度增殖和侵袭，部分或完全阻断激动剂的作用。此外，GPR30的RNA和蛋白表达均被G1、E2或OHT上调。本研究为探讨子宫兴奋作用的机制提供了新的思路。(C)2012 Elsevier Inc.保留所有权利。
The selective ER modulator tamoxifen (TAM(1)) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17 beta-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in he agonistic activity exerted by TAM in the uterus. (C) 2012 Elsevier Inc. All rights reserved.