Determining the Effects of the Environmental Estrogens Bisphenol A and Methylparaben in MCF7 Cells

Estrogens are responsible for stimulating the growth of a large percentage of breast cancers through activation of estrogen receptor alpha (ERα). Bisphenol A (BPA), xenoestrogen found in plastics, is believed to have the same effect that ERa has on mammary cells, although this hypothesis has not been proven. Methylparaben  (mePB), a common preservative, has also been found to have estrogenic effects. We hypothesize that bisphenol A and methylparaben have estrogenic effects in human breast cells. To test this hypothesis, we will assess the effects of these molecules directly on ERα responsive MCF7 breast cancer cells. We illustrate that in vitro studies at 10 nM concentrations, while only 17b-estradiol (E2) enhances proliferation of MCF7 cells, E2, BPA and mePB increase mammosphere size. Furthermore, E2, BPA and mePB enhance expression of hPS2 in mammospheres assays. FACS analysis reveals that breast cancer stem cell marker aldehyde dehydrogenase (ALDH) is enhanced in both E2 and mePB-treated MCF7 cells. These results suggest that estrogen and xenoestrogens enhance expression of cancer stem cell markers known to be associated with poor outcome survival and metastasis in ERα⁺-breast cancer patients. Future studies, utilizing chromatin immunoprecipitations (ChIP) will provide insights to the mechanism by which xenoestrogens exert gene activation mediated through ERα recruitment to specific-gene targets. Future studies will also utilize in vivo xenograph modeling with MCF7 cells treated E2, BPA and mePB in nude mice, which will reveal tumor growth kinetics. Our studies will provide insights into environmental xenoestrogens effects on the behavior of ERα⁺ breast cancer.