Bisphenol A prevents MCF‐7 breast cell apoptosis via the inhibition of progesterone receptor transactivation

Abstract

Abstract2,2‐Bis(4‐hydroxyphenyl)propane (bisphenol A; BPA) is an environmental endocrine‐disrupting chemical. It mimics the effects of estrogen at multiple levels by activating estrogen receptors (ERs); however, BPA also affects the proliferation of human breast cancer cells independent of ERs. Although BPA inhibits progesterone (P4) signaling, the toxicological significance of its effects remain unknown. Tripartite motif‐containing 22 (TRIM22) has been identified as a P4‐responsive and apoptosis‐related gene. Nevertheless, it has not yet been established whether exogenous chemicals change TRIM22 gene levels. Therefore, the present study investigated the effects of BPA on P4 signaling and TRIM22 and TP53 expression in human breast carcinoma MCF‐7 cells. In MCF‐7 cells incubated with various concentrations of P4, TRIM22 messenger RNA (mRNA) levels increased in a dose‐dependent manner. P4 induced apoptosis and decreased viability in MCF‐7 cells. The knockdown of TRIM22 abolished P4‐induced decreases in cell viability and P4‐induced apoptosis. P4 increased TP53 mRNA expression and p53 knockdown decrease the basal level of TRIM22 and P4 increased TRIM22 mRNA expression independent of p53 expression. BPA attenuated P4‐induced increases in the ratio of cell apoptosis in a concentration‐dependent manner, and the P4‐induced decreases in cell viability was abolished in the presence of 100 nM and higher BPA concentrations. Furthermore, BPA inhibited P4‐induced TRIM22 and TP53 expression. In conclusion, BPA inhibited P4‐induced apoptosis in MCF‐7 cells via the inhibition of P4 receptor transactivation. TRIM22 gene has potential as a biomarker for investigating the disruption of P4 signaling by chemicals.