Journal of Nutrition, 2012, 142(7):1382S-8S.

Altered Carcinogenesis and Proteome in Mammary Glands of Rats after Prepubertal Exposures to the Hormonally Active Chemicals Bisphenol A and Genistein

Angela M. Betancourt, Jun Wang, Sarah Jenkins, et al

Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA; et al

Through our diet, we are exposed to numerous natural and man-made chemicals, including polyphenols with hormone-like properties. The most abundant hormonally active polyphenols are characterized as weak estrogens. These chemicals are hypothesized to interfere with signaling pathways involved in important diseases such as breast cancer, which in most cases is initially estrogen dependent. Two such chemicals are bisphenol A (BPA), a plasticizer, and genistein, a component of soy. In spite of both possessing estrogenic properties, BPA and genistein yield different health outcomes. The exposure of rats during the prepubertal period to BPA increases the susceptibility of adult animals for mammary cancer development, whereas genistein decreases this susceptibility in a chemically induced model. Because both BPA and genistein possess estrogenic properties, it is certainly plausible that additional mechanisms are affected by these chemicals. Hence, it was our goal to investigate at the protein level how exposure to these 2 chemicals can contribute to mammary cancer causation as opposed to cancer chemoprevention. Using 2-dimensional gel electrophoresis followed by MS analysis, we identified differentially regulated proteins from the mammary glands of rats prepubertally exposed to BPA and genistein. Following protein identification, we used immunoblotting techniques to validate the identity and regulation of these proteins and to identify downstream signaling proteins. Our studies highlight the importance of proteomics technology in elucidating signaling pathways altered by exposure to hormonally active chemicals and its potential value in identifying biomarkers for mammary cancer.

美国《营养学报》，2012年7月

在青春期前暴露于激素活性化学物质双酚 A 和金雀异黄素以后大鼠乳腺增生病的变异细胞癌变和蛋白质组学

安吉拉 M 贝当古，王俊，莎拉  詹金斯，等

美国阿拉巴马大学伯明翰分校药理学和毒理学学院等

通过我们的饮食，我们都接触到许多天然和人造化学物质，包括具有激素属性的茶多酚。最丰富的激素性活性多酚的特点为弱雌激素。假设这些化学物质，干扰参与重要的疾病的信号通路，例如乳腺癌，其在大多数情况下最初是依赖雌激素的。这两种化学物质是双酚 A (BPA)、一种增塑剂 和金雀异黄素、 大豆的一种组成部分。尽管两者都具有雌激素的属性， 双酚 A 和金雀异黄素得到不同的健康结果。在青春期以前时期间大鼠暴露于双酚 A 增强了成年大鼠对乳腺癌发展的易感性，而金雀异黄素则以化学诱导模式降低了这种易感性。因为双酚 A 和金雀异黄素具有雌激素特性，额外机制受这些化学物质影响是有道理的。因此，我们的目标是探究接触这2种 化学试剂的蛋白质水平有助于乳腺癌的产生，而不是癌症的化学预防。使用MS 分析和二维凝胶电泳，我们确定了暴露于双酚 A 和金雀异黄素的青春期前大鼠乳腺蛋白的差异性调节。在确认蛋白质后，我们使用免疫印迹技术确认了这些蛋白质的名称和调节并确定了下游的信号蛋白。我们的研究强调了蛋白质组学技术在阐明暴露于激素活性的化学物质改变信号转导通路方面的重要性以及其在识别乳腺癌生物标志物方面潜在的价值。