Loss of BRCA1 leads to an increased sensitivity to Bisphenol A.
Humans are chronically exposed to the plasticizer, Bisphenol A (BPA), that can adversely affect the normal hormonal regulation of cellular functions by mimicking the actions of estrogen. This biological response to BPA may vary according to an individual's genetic characteristics (e.g., BRCA1 mutations or deletion). In this study, both cell culture and mouse models were used to elucidate whether the loss of BRCA1 function could affect BPA-mediated cell proliferation. In studies using BPA levels comparable to human exposures, we found that loss of BRCA1 enhances BPA-induced cell proliferation in both systems. In vitro, we found that loss of BRCA1 enhances BPA-induced ERα signaling. In vivo, we found that BPA administration stimulates mammary gland epithelial tissue/cell proliferation leading to hyperplasia in Brca1 mutant mice compared to wild-type control mice. These results suggest that the biological responses in BRCA1-deficient cells may depend on environmental exposures, specifically BPA.
Jones
Laundette P
LP
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, MD 21201, USA. ljone010@umaryland.edu
Sampson
Aishia
A
Kang
Hyo Jin
HJ
Kim
Hee Jeong
HJ
Yi
Yong-Weon
YW
Kwon
Sun Young
SY
Babus
Janice K
JK
Wang
Antai
A
Bae
Insoo
I
D000818:Animals; D019313:BRCA1 Protein / Q000502:physiology*; D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000502:physiology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000633:toxicity*; D013629:Tamoxifen / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D019313:BRCA1 Protein; D001559:Benzhydryl Compounds; D004958:Estradiol; D047628:Estrogen Receptor alpha; D000077267:Fulvestrant; D010636:Phenols; D013629:Tamoxifen; C006780:bisphenol A; D000098826:Bisphenol A Compounds