Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells

Abstract

Xenoestrogens such as bisphenol-A (BPA) can mimic endogenous 17β-estradiol (E2) in vitro and in vivo through binding the estrogen receptor (ER), and modulating target gene expression. In the present study, we compared global gene regulation by BPA and E2 in estrogen responsive (ERα-HA) human breast cancer cells derived from the MCF-7 cell line. The ERα-HA cells (stably over-expressing ERα) were exposed to E2 (10 −8 M) or BPA (10 −6 M), for 3 h followed by analysis of global gene expression. More than 40 transcripts were significantly changed in ERα-HA cells, with many being unique to BPA. At least 15 genes were modulated by BPA in the ER-null C4–12 cell line, indicating ER independent activity. Utilizing quantitative reverse transcription-polymerase chain reaction (RT-PCR), we confirmed BPA and E2 mediated regulation of four selected genes. A consensus Alu-type estrogen responsive element (ERE) was found in the Wiskott–Aldrich syndrome protein (WASP) gene, which conferred responsiveness to BPA and E2 in a reporter gene assay. Significant stimulation was seen only in ERα expressing cells, thus indicating a functional ERE. Taken together these data illustrate novel gene regulation by BPA and E2, which has implications for in vivo actions and previous reports of additive and synergistic effects on breast cancer cell growth.