Abstract 2124: Analysis of FAM111A, a newly identified AR regulated gene, in prostate cancer

Abstract

Abstract Prostate carcinoma (PCa) is the most commonly diagnosed cancer in men in the United States. Most PCas are dependent on the androgen receptor (AR) for growth and survival, and this dependency is exploited as androgen deprivation is the major therapeutic intervention. However, PCa inevitably progress to become castration resistant, yet remain reliant on the activity of the AR. Further understanding the mechanisms that mediate castration resistance and the pathways downstream of the AR will enhance our ability to treat this stage of the disease. RNA-seq studies of two castrate resistant cell lines following AR ablation identified a number of transcripts that were AR regulated. The studies identified FAM111A as an AR regulated gene. While little is known about FAM111A, a previous study has shown that the FAM111A gene harbors a PCa susceptibility SNP and that the FAM111A protein interacts with SV40 T-Ag. Our studies indicate that AR represses FAM111A in cell culture and xenograft models of CaP. Additionally, the expression of the only known FAM111A paralogue, FAM111B, was reciprocally regulated in cell lines and in the xenograft. FAM111A is expressed in all cultured prostate derived cell lines we looked at, and we found that there are two FAM111A isoforms. Furthermore, a siRNA mediated ablation of FAM111A modified apoptotic responses to chemotherapeutic stimuli. An immunohistochemical analysis of a prostate tumor tissue array was used to assess the expression of FAM111A. FAM111A is expressed in the cytoplasmic and nuclear compartments and expression in the cytoplasmic compartment in non-tumor prostate tissue is higher than in adjacent tumor cells. In conclusions, FAM111a is an AR regulated gene, has been associated with PCa in a GWAS study, interacts with the SV40 T-antigen and is expressed at lower levels in tumor cells. This suggests that FAM111A may be have a role in prostate tumorigenesis. Citation Format: Maria Mudryj, Stephen J. Libertini, Alan P. Lombard, Salma Saddiqui, Paramita M. Ghosh. Analysis of FAM111A, a newly identified AR regulated gene, in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2124. doi:10.1158/1538-7445.AM2014-2124