The modulatory role of low concentrations of bisphenol A on tamoxifen-induced proliferation and apoptosis in breast cancer cells

Selective estrogen receptor modulators such as tamoxifen (TAM) significantly reduce the risks of developing estrogen receptor-positive (ER+) breast cancer. Low concentrations (nanomolar range) of bisphenol A (BPA) shows estrogenic effects and further promotes the proliferation of hormone-dependent breast cancer cells. However, whether or not BPA can influence TAM-treatment resistance in breast cancer has not drawn much attention. In the current study, low concentrations of BPA reduced TAM-induced cytotoxicity of MCF-7 cells, which was proved by the suppression of cell apoptosis, transition of cell cycle from G1 to S phase, and upregulation of cyclin D1 and ER. Simultaneously, the mRNA levels of estrogen-related receptor (ERR) and its coactivators, peroxisome proliferation-activated receptor coactivator-1 (PGC-1), and PGC-1, were increased. However, the similar effects were not observed in MDA-MB-231 cells. Our results indicated that low concentrations of BPA decreased the sensitivity of TAM in MCF-7 cells rather than in MDA-MB-231 cells. These different actions likely involved the interaction of relative receptors and coactivators. This study provided a possible support that the exposure of BPA in environmental media may potentially induce TAM resistance to breast cancer treatment.