The modulatory role of low concentrations of bisphenol A on tamoxifen-induced proliferation and apoptosis in breast cancer cells
Environmental science and pollution research international(2018)
摘要
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 ERα. Simultaneously, the mRNA levels of estrogen-related receptor γ (ERRγ) and its coactivators, peroxisome proliferation–activated receptor γ coactivator-1α (PGC-1α), and PGC-1β, 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.
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关键词
Bisphenol A,Breast cancer cells,Cell viability,Estrogen-related receptors,Tamoxifen
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