Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
J Nutr. 2012 Jul;142(7):1382S-8S. doi: 10.3945/jn.111.152058. Epub 2012 May 30.
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.
通过我们的饮食，我们会接触到许多天然和人工合成的化学物质，包括具有激素样特性的多酚。最丰富的具有激素活性的多酚被认为是弱雌激素。这些化学物质被假设会干扰与重要疾病（如乳腺癌）相关的信号通路，而在大多数情况下，乳腺癌最初是依赖雌激素的。两种这样的化学物质是双酚 A（BPA），一种增塑剂，和染料木黄酮，大豆的一种成分。尽管两者都具有雌激素特性，但 BPA 和染料木黄酮产生不同的健康结果。在青春期前阶段暴露于 BPA 会增加成年动物患乳腺癌的易感性，而在化学诱导模型中，染料木黄酮会降低这种易感性。由于 BPA 和染料木黄酮都具有雌激素特性，因此可以肯定的是，这些化学物质还会影响其他机制。因此，我们的目标是在蛋白质水平上研究暴露于这两种化学物质如何导致乳腺癌的发生，而不是化学预防。我们使用二维凝胶电泳和 MS 分析，从青春期前暴露于 BPA 和染料木黄酮的大鼠的乳腺中鉴定出差异调节的蛋白质。在鉴定蛋白质后，我们使用免疫印迹技术来验证这些蛋白质的身份和调节，并确定下游信号蛋白。我们的研究强调了蛋白质组学技术在阐明暴露于具有激素活性的化学物质后改变的信号通路方面的重要性，及其在鉴定乳腺癌生物标志物方面的潜在价值。
