摘要:Ba c k g r o u n d: Bisphenol A (BPA) is the principal co nstituent of ba by bottles, reusable water bottles, metal cans, and pla stic food containers. BPA exerts estrogen-like activity by inter acting with the classical estrogen receptors (ERαand ERβ) and through the G protein-coupled receptor (GPR30/GPER). In this regard, recent studies have shown that GPER was involved in the prolifera-tive effects induced by BPA in both normal and tumor cells.oB j e c t i v e s: We studied the transduction signaling pathways through which BPA influences cell proliferation and migration in human breast cancer cells and cancer-associated fibroblasts (CAFs).Me t h o d sa n dr e s u l t s: We used as a model system SKBR3 breast cancer cells and CAFs that lack the classical ERs. Specific pharmacological inhibitors and gene-silencing procedures were used to show that BPA induces the expression of the GPER target genes c-FOS, EGR.1, and CTGF through the GPER/EGFR/ERK transduction pathway in SKBR3 breast cancer cells and CAFs. Moreover, we observed that GPER is required for growth effects and migration stimulated by BPA in both cell types.co n c l u s i o n s: Results indicate that GPER is involved in the biological action elicited by BPA in breast cancer cells and CAFs. Hence, GPER-mediated signaling should be included among the transduction mechanisms through which BPA may stimulate cancer progression
关键词:bisphenol A; breast cancer cells; cancer-associated fibroblasts; GPR30/GPER; tumor ;micro ;environment