The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

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• 作者：Gui-Qiang Du^a ; Long Zhou^a ; Xiao-Yue Chen^a ; Xiao-Ping Wan^a ; ^{wanxiaoping61@126.com} ; Yin-Yan He^b
• 关键词：Endometrial cancer ; GPR30 ; Tamoxifen ; Hydroxytamoxifen
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：6 April, 2012
• 卷：420
• 期：2
• 页码：343-349
• 文件大小：1192 K

摘要

The selective ER modulator tamoxifen (TAM) 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尾-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 the agonistic activity exerted by TAM in the uterus.