Bisphenol A alone or in combination with estradiol modulates cell cycle- and apoptosis-related proteins and genes in MCF7 cells

Abstract

Bisphenol A (BPA) with its estrogenic properties is intensively studied since its presence in the environment and human body. Besides other adverse effects, the compound is suspected of contributing to hormone-related cancers. The present study was aimed to investigate short time (24 h) effects of BPA on the important genes/proteins involved in apoptosis and the cell cycle progression in the breast cancer cells MCF7. The experimental design covered cell treatment with a broad BPA concentration scale: 10-12M corresponding to ubiquitous exposure, 10-9M relevant to human levels, and 10-6M as experimentally usual. We further investigated the combined effects of low BPA dose (10-12M) with physiological concentration of estradiol (E2) (10-9M). The expression of particular proteins and genes was studied by Western blotting and real time RT-PCR, respectively. Estrogenic effect of BPA was confirmed in the following checkpoints: mRNA expression of estrogen receptor α, expression of cyclin D1 and A2 proteins and CCNA2 gene, Bax and Bcl2 protein levels. For both cyclins protein levels, the maximum stimulation was present at 10-9M BPA and the effects resembled the "inverted U"-shape, a nonmonotonic dose-response curve reported for the action of xenoestrogens. The combined effect of low BPA dose with physiological E2 concentration differ from those of individual compounds, the character of stimulatory response is neither additive nor synergistic. The results obtained strongly support the evidence of BPA and BPA+E2 proliferation-promoting effects in human breast carcinoma cells, even after short time exposure, partially via reduced rate of apoptosis by the action of BPA+E2.