Increase in the levels of chaperone proteins by exposure to β-estradiol, bisphenol A and 4-methoxyphenol in human cells transfected with estrogen receptor α cDNA

We examined changes in the levels of chaperone proteins to evaluate the toxic effects of environmental chemicals in human cells in vitro. Some chaperones are up-regulated by estrogenic chemicals, but the effect is not necessarily dependent on the receptor. Thus we also investigated whether a chemical-induced change in chaperone protein expression is human estrogen receptor (hER)-dependent or not, using cultured human cell lines transfected with hERα cDNA or an empty vector. In the hERα-expressed cells, the protein levels of the heat shock protein 27 (HSP27), the glucose-regulated protein 78 (GRP78/BiP), and GRP94 increased after exposure to β-estradiol (E2) (from 10−9 M to 10−6 M) and bisphenol A (BPA) (from 10−6 M to 10−5 M). On the other hand, the increase was not observed in the cells without hERα expression. These results suggest that the E2- and BPA-induced increase in the protein levels were hERα dependent. We next examined the effect of four phenolic chemicals similar in structure to BPA, and found that among them, 4-methoxyphenol (from 10−6 M to 10−5 M) increased the levels of the chaperone proteins with hERα dependency. Thus the human cultured cells would be suitable for evaluating whether an increase in chaperone proteins occurs upon exposure to environmental chemicals and whether the effect is ER-dependent.