Abstract 2400: Tumor suppressor EAF2 cooperates with p53 in control of prostate tumorigenesis and vascularity

Introduction: Inactivation of EAF2 has been shown previously to lead to tumorigenesis in multiple organs; however the mechanism of EAF2 tumor suppression remains unclear. Demonstrating functional interactions between p53 and EAF2 would link the newly discovered tumor suppressor EAF2 to the well-established p53 pathway, providing new insights into the mechanisms of p53 and EAF2 action. We previously have shown that EAF2 can co-localize and co-immunoprecipitate with p53 in transfected cells. In a TSP-1 promoter-driven luciferase reporter assay, p53 transfection suppressed the TSP-1 promoter activity and EAF2 co-transfection blocked the p53 suppression of TSP-1 promoter. However, EAF2 transfection alone had little or no effect on the TSP-1 promoter. In a murine model, EAF2 knockout caused TSP-1 down-regulation, supporting an in vivo role for EAF2 in regulation of TSP-1 expression. Methods: Mouse knockout, transient transfection, co-localization, co-immunoprecipitation, and luciferase-based promoter assay were employed in this study. Results: Ongoing animal studies show that loss of EAF2 and p53 displayed much more dramatic phenotypes than loss of EAF2 or p53 individually and resulted in more severe splenic extramedullary hematopoiesis, and further increased vessel density in the prostate and liver. Furthermore, double knockout of EAF2 and p53, but not knockout of EAF2 or p53 alone, resulted in prostate tumorigenesis. Conclusion: The above observations together suggest that EAF2 and p53 cooperate in prostate tumorigenesis and increased vascularity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2400. doi:10.1158/1538-7445.AM2011-2400