Loss of BRCA1 leads to an increased sensitivity to Bisphenol A.
Loss of BRCA1 leads to an increased sensitivity to Bisphenol A.
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DOI：
10.1016/j.toxlet.2010.09.008
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发表时间：
2010-12-15
影响因子：
3.5
通讯作者：
Bae, Insoo
中科院分区：
文献类型：
--
作者：
Jones, Laundette P.;Sampson, Aishia;Kang, Hyo Jin;Kim, Hee Jeong;Yi, Yong-Weon;Kwon, Sun Young;Babus, Janice K.;Wang, Antai;Bae, Insoo
人类长期接触增塑剂双酚A(BPA)，这种增塑剂会模仿雌激素的作用，对细胞功能的正常激素调节产生不利影响。这种对BPA的生物反应可能会因个体的遗传特征(例如BRCA1突变或缺失)而有所不同。在这项研究中，细胞培养和小鼠模型被用来阐明BRCA1功能的丧失是否会影响BPA介导的细胞增殖。在使用与人类暴露水平相当的BPA水平进行的研究中，我们发现BRCA1的缺失在两个系统中都增强了BPA诱导的细胞增殖。在体外，我们发现BRCA1的缺失增强了双酚A诱导的ERα信号转导。在体内，我们发现双酚A注射刺激乳腺上皮组织/细胞增殖，导致BRCA1突变小鼠与野生型对照小鼠相比出现增殖。这些结果表明，BRCA1缺陷细胞的生物学反应可能依赖于环境暴露，特别是BPA。
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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影响因子：
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