Abstract 4302: AR signaling promotes prostate carcinogenesis

Abstract

Abstract Prostate cancer (PCa) is the most common non-skin cancer in American men. Each year, about 164,690 new patients will be diagnosed and about 29,430 men will die from this disease in 2018. Studies have identified several factors that increase the risk of PCa, including age, race, family history, and some diet factors. However, the exact cause of PCa remains unclear. Prostate is an androgen dependent organ and the growth of PCa also dependents on androgen and AR signaling. It is well established that AR signaling is the central player in promoting PCa progression. Here, we explore if AR signaling also plays a role in prostate carcinogenesis. We found that activation of AR signaling in normal prostate epithelial cells suppressed their cell proliferation in vitro but induced carcinogenesis in vivo. To explore the mechanisms that contribute to the differential effects of AR in vitro and in vivo, we examined if AR signaling induces genome instability in prostate epithelial cells, resulting in carcinogenesis and tumor progression. Senescence-associated beta-galactosidase staining results indicated that androgen treatment induced cellular senescence of prostate epithelial cells. Also, we found that the cells that survived the cellular senescence had altered genome ploidy and increased expression of active DNA-PK, suggesting that non-homologous end joining repair pathway is active in these cells. Our data support that AR signaling promotes genome instability in prostate epithelial cells, contributing to carcinogenesis. This may explain the high frequency of cancer developed in hormone-regulated organs such as prostate, mammary gland, and liver. Funding: This study was supported by: FWCC/Foundation Legacy Funds, DOD New Investigator Award, The Office of Research SEED awards, The Department of Biochemistry & Molecular Biology. Citation Format: Siyuan Cheng, Shu Yang, Zachary M. Connelly, Fenghua Chen, Xiuping Yu. AR signaling promotes prostate carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4302.