Set, a Putative Oncogene, As a Biomarker for Prenatal Exposure to Bisphenol A

Background: Bisphenol A (BPA), an endocrine disrupting chemical, has been suspected to posecarcinogenic risks. However, likely mechanisms are obscure and there are difficulties to estimating its realsignificance for cancer development.
Methods: We therefore studied BPA-induced proteomic alterations inimmune organs of ICR mice offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinkingwater). We performed 2D-gel analyses of samples, considering differences in spleen, exposure levels, sex,and ages.
Results: From proteomic analyses, we found various proteins were up- or down-regulated byBPA. Among them, SET, a putative oncogene and inhibitor of phosphatase 2A, was significantly downregulatedin a BPA dose-dependent manner. We also confirmed down-regulation of SET in western blotand real time PCR analyses. From gene network analysis, SET is predicted to communicate with othergenes including CYP17, which is involved in biosynthesis and metabolism of sex-hormones.
Conclusions:This study provided evidence that SET can be applied as a new biomarker for prenatal BPA exposure andsuggests a potential new mechanism of action in that BPA may disrupt CYP17 via SET.