Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells.
Xenoestrogens such as bisphenol-A (BPA) can mimic endogenous 17beta-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 (ERalpha-HA) human breast cancer cells derived from the MCF-7 cell line. The ERalpha-HA cells (stably over-expressing ERalpha) were exposed to E2 (10(-8)M) or BPA (10(-6)M), for 3h followed by analysis of global gene expression. More than 40 transcripts were significantly changed in ERalpha-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 ERalpha 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.
Singleton
David W
DW
Department of Cell Biology, Neurobiology and Anatomy, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.
Feng
Yuxin
Y
Chen
Yangde
Y
Busch
Steve J
SJ
Lee
Adrian V
AV
Puga
Alvaro
A
Khan
Sohaib A
SA
D020087:Alu Elements / Q000235:genetics; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D005810:Multigene Family / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000494:pharmacology*; D020218:Response Elements / Q000187:drug effects* / Q000235:genetics; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047908:Intracellular Signaling Peptides and Proteins; D010636:Phenols; C109903:WIPF1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds