Bisphenol A and estrogen induce proliferation of human thyroid tumor cells via an estrogen-receptor-dependent pathway

Objective: To determine the relationship between papillary thyroid carcinoma and environmental exposure to bisphenol A (BPA) or 17-beta estrogen (E-2) by assessing the effects of these compounds on estrogen receptor expression and AICT/mTOR signaling. Methods: The effects of low levels of BPA (1mM-10nM) and 17 beta-estradiol (E-2, 0.1mM-1nM) on ER expression and cellular proliferation were determined in human thyroid papillary cancer BHP10-3 cells. Protein and mRNA levels of estrogen nuclear receptors (Ell alpha/ER beta) and membrane receptors (GPR30) were determined by immunofluorescence assay, Western blotting, and RT-PCR, respectively, and proliferation was assessed by CCK-8 assay. Results: The proliferative effects of BPA and E-2 were both concentration- and time-dependent. Expression of ER alpha/ER beta and GPR30 were enhanced by BPA and E-2, BPA and E-2 could quickly phosphorylate AKT/mTOR. Moreover, ICI suppressed ER alpha expression and activated GPR30 as did G-1. G-15 reversed the effects of E-2 on GPR30 and AKT/mTOR, but did not alter the effect of BPA. Conclusions: BPA influences thyroid cancer proliferation by regulating expression of ERs and GPR30, a mechanism that differs from E-2. In addition, ICI and G-15 may have the potential to be used as anti thyroid cancer agents. (C) 2017 Elsevier Inc. All rights reserved.