title: The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai, China.
authors.forename: Gui-Qiang
authors.initials: GQ
authors.lastname: Du
authors.forename: Long
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Chen
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wan
authors.forename: Yin-Yan
authors.initials: YY
authors.lastname: He
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives*; D015854:Up-Regulation
chemical_list: C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C016601:afimoxifene