The G protein-coupled receptor GPR30 binds 17β-estradiol (E 2 ) yet differs from classic estrogen receptors (ERα and ERβ). GPR30 can mediate E 2 -induced nongenomic signaling, but its role in ERα-positive breast cancer remains unclear. Gene expression microarray data from five cohorts comprising 1,250 breast carcinomas showed an association between increased GPR30 expression and ERα-positive status. We therefore examined GPR30 in estrogenic activities in ER-positive MCF-7 breast cancer cells using G-1 and diethylstilbestrol (DES), ligands that selectively activate GPR30 and ER, respectively, and small interfering RNAs. In expression studies, E 2 and DES, but not G-1, transiently downregulated both ER and GPR30, indicating
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