204 ALTERED GENE EXPRESSION FOLLOWING EXPOSURE TO BISPHENOL A IN HUMAN OVARIAN CANCER CELLS EXPRESSING ESTROGEN RECEPTORS BY MICROARRAY

Abstract

Although endocrine-disrupting chemicals (EDC) may interfere with the endocrine system(s) of animals and humans and have an estrogenicity or androgenicity, the exact mechanism(s) underlying their detrimental effects is not clearly understood. Among them, bisphenol A (BPA) is widespread in the environment and is commonly ingested by animals because it is used in the manufacture of polycarbonate plastics, food-storage containers, and other plastics. Thus, in this study, we evaluated altered gene expression following exposure to BPA by microarry in human ovarian cancer cells, which highly express oestrogen receptors (ER). Treatment with BPA and endogenous oestrogen (E₂) for 24 h resulted in an increase in cell proliferation and enhanced the oestrogen response element (ERE) activity in human BG-1 ovarian cancer cells with ER. Bisphenol A-induced cell growth and the activation of ERE were reversed by an oestrogen receptor antagonist, ICI 182 780, suggesting that ER appear to be involved in BPA-induced cell growth and ERE activation in these ovarian cells. Following BPA treatment, the expression levels of representative genes, namely, apoptosis inhibitor 4 (survivin), RAB31 ras oncogene family, v-myc, v-myb, cyclin A2, cyclin B1, amphiregulin, insulin-like growth factor binding protein 4, chemokine-like factor 3, fibroblast growth factor, and E₂F transcription factor 4, were subsequently confirmed in these ovarian cells by real-time PCR. Taken together, these results indicate distinctly altered expression of responsive genes following exposure to BPA, and implicate distinct effects of endogenous E₂ and environmental EDC in human ovarian cancer cells expressing ER.