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

  • Lee, Ho-Sun (Research Center for Cell Fate Control, College of Pharmacy Sookmyung Women's University) ;
  • Pyo, Myoung-Yun (Research Center for Cell Fate Control, College of Pharmacy Sookmyung Women's University) ;
  • Yang, Mi-Hi (Research Center for Cell Fate Control, College of Pharmacy Sookmyung Women's University)
  • Published : 2012.06.30


Background: Bisphenol A (BPA), an endocrine disrupting chemical, has been suspected to pose carcinogenic risks. However, likely mechanisms are obscure and there are difficulties to estimating its real significance for cancer development. Methods: We therefore studied BPA-induced proteomic alterations in immune organs of ICR mice offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinking water). 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 by BPA. Among them, SET, a putative oncogene and inhibitor of phosphatase 2A, was significantly down-regulated in a BPA dose-dependent manner. We also confirmed down-regulation of SET in western blot and real time PCR analyses. From gene network analysis, SET is predicted to communicate with other genes 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 and suggests a potential new mechanism of action in that BPA may disrupt CYP17 via SET.


Supported by : National Research Foundation of Korea (NRF)


  1. Belcher SM, Le HH, Spurling L, et al (2005). Rapid estrogenic regulation of extracellular signal- regulated kinase 1/2 signaling in cerebellar granule cells involves a G protein- and protein kinase A-dependent mechanism and intracellular activation of protein phosphatase 2A. Endocrinology, 146, 5397-406.
  2. Bradford MM (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-54.
  3. Christensen DJ, Chen Y, Oddo J, et al (2011). SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target. Blood, 118, 4150-8.
  4. Dolinoy DC, Huang D, Jirtle RL (2007). Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A, 104, 13056-61.
  5. Engel SM, Levy B, Liu Z, et al (2006). Xenobiotic phenols in early pregnancy amniotic fluid. Reprod Toxicol, 21, 110-2.
  6. Kuroda N, Kinoshita Y, Sun Y, et al (2003). Measurement of bisphenol A levels in human blood serum and ascitic fluid by HPLC using a fluorescent labeling reagent. J Pharm Biomed Anal, 30, 1743-9.
  7. Lakind JS, Naiman DQ (2008). Bisphenol A (BPA) daily intakes in the United States: estimates from the 2003-2004 NHANES urinary BPA data. J Expo Sci Environ Epidemiol, 18, 608-15.
  8. Lamason R, Zhao P, Rawat R, et al (2006). Sexual dimorphism in immune response genes as a function of puberty. BMC Immunol , 7, 2.
  9. Mellon SH, Bair SR, Depoix C, et al (2007). Translin coactivates steroidogenic factor-1-stimulated transcription. Mol Endocrinol, 21, 89-105.
  10. Prins GS, Birch L, Tang WY, et al (2007). Developmental estrogen exposures predispose to prostate carcinogenesis with aging. Reprod Toxicol, 23, 374-82.
  11. Rubin MM (2007). Antenatal exposure to DES: lessons learned future concerns. Obstet Gynecol Surv, 62, 548-55.
  12. Safe S, McDougal A (2002). Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers. Int J Oncol , 20, 1123-8.
  13. Simon V, Oner SS, Cohen-Tannoudji J, et al (2012). Influence of the Accessory Protein Set on M3 Muscarinic Receptor Phosphorylation and G Protein Coupling. Mol Pharmacol, doi:10.1124/mol.111.075523.
  14. von Lindern M, van Baal S, Wiegant J, et al (1992). Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene. Mol Cell Biol, 12, 3346-55.
  15. Yang M, Kim SY, Chang SS, et al (2006). Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity and effect and endocrine-related health effects. Environ Mol Mutagen, 47, 571-8.
  16. Yang M, Lee HS, Pyo MY (2008). Proteomic biomarkers for prenatal bisphenol A-exposure in mouse immune organs. Environ Mol Mutagen, 49, 368-73.
  17. Ye L, Zhao B, Hu G, et al (2011). Inhibition of human and rat testicular steroidogenic enzyme activities by bisphenol A. Toxicol Lett, 207, 137-42.
  18. Ye X, Kuklenyik Z, Needham LL, et al (2006). Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switchinghigh performance liquid chromatography-isotope dilution tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci, 831, 110-5.
  19. Yi B, Kasai H, Lee HS, et al (2011). Inhibition by wheat sprout (Triticum aestivum) juice of bisphenol A-induced oxidative stress in young women. Mutat Res, 724, 64-8.
  20. Yi B, Kim C, Yang M (2010). Biological monitoring of bisphenol A with HLPC/FLD and LC/MS/MS assays. J Chromatogr B Analyt Technol Biomed Life Sci, 878, 2606-10.
  21. Zhang P, Compagnone NA, Fiore C, et al (2001). Developmental gonadal expression of the transcription factor SET and its target gene, P450c17 (17alphahydroxylase/c17, 20 lyase). DNA Cell Biol, 20, 613-24.

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