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

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.