The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells
Biochemical and Biophysical Research CommunicationsPublished 8 March 2012
Guiqiang Du, Long Zhou, Xiaoyue Chen, Xiaoping Wan, Yinyan He
Citations70
SJR quartileQ2
SJR score0.75
SNIP0.56
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TL;DR
New insight is provided into the mechanism involved in the agonistic activity exerted by TAM in the uterus through the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer.
Abstract
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, 17β-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.
Keywords
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