Loss of BRCA1 leads to an increased sensitivity to Bisphenol A |
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| Authors: | Laundette P Jones Aishia Sampson Hyo Jin Kang Hee Jeong Kim Yong-Weon Yi Sun Young Kwon Janice K Babus Antai Wang Insoo Bae |
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| Institution: | 1. Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, MD 21201, United States;2. Department of Oncology Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, United States;3. Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, United States;4. WCU (World Class University) Research Center of Nanobiomedical Science, Dankook University, Cheonan, South Korea;5. Department of Pathology, Keimyung University, Dongsan-Dong, Deagu, South Korea;6. Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, United States;g Department of Biostatistics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, United States |
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| Abstract: | 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. |
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| Keywords: | Brca1 breast cancer susceptibility gene 1 BPA bisphenol A ERα estrogen receptor alpha |
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