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.
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Authors | Gui-Qiang Du, Long Zhou, Xiao-Yue Chen, Xiao-Ping Wan, Yin-Yan He |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 420
Issue 2
Pg. 343-9
(Apr 06 2012)
ISSN: 1090-2104 [Electronic] United States |
PMID | 22425989
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- GPER1 protein, human
- Receptors, Estrogen
- Receptors, G-Protein-Coupled
- Selective Estrogen Receptor Modulators
- Tamoxifen
- afimoxifene
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Topics |
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Endometrial Neoplasms
(chemically induced, metabolism, pathology)
- Female
- Humans
- Neoplasm Invasiveness
- Receptors, Estrogen
(metabolism)
- Receptors, G-Protein-Coupled
(metabolism)
- Selective Estrogen Receptor Modulators
(adverse effects)
- Tamoxifen
(adverse effects, analogs & derivatives)
- Up-Regulation
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