AKIRIN2, DLGAP5 and NSFL1C are Candidate Aggressive Prostate Cancer Susceptibility Genes

Science Center, Bent Corridor

Prostate cancer (PC) is the most common non-cutaneous malignancy in men, with 220,000 new cases expected in 2015 alone. However, only about 13% of PC cases are fatal. Approximately 25-30% of men who die from PC develop tumors characterized by neuroendocrine (NE) features. We previously used a systems genetics approach using the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of aggressive NE PC to identify AKIRIN2, DLGAP5, and NSFL1C as aggressive PC susceptibility genes. The goal of this study is to functionally characterize these genes, in order to determine how they influence susceptibility to aggressive PC. To study the function of these genes in vitro, the LNCaP human prostate cancer cell line was stably transfected with one of these three genes using lentiviral-mediated transduction. Quantitative real-time PCR (qPCR) was used to detect the levels of known NE markers associated with aggressive PC, which demonstrated that AKIRIN2 and NSFL1C enhance the expression of several such markers. Colony formation in soft agar suspension was quantified for each of the cell lines, which demonstrated that AKIRIN2, DLGAP5, and NSFL1C enhance anchorage independent growth. Finally, a trans-well migration assay demonstrated that each of these three genes significantly impacts both cell migration and invasion, which are growth properties commonly associated with metastasis. Results from our in vitro studies indicate that these three genes may play a role in susceptibility to aggressive PC. By deciphering the roles of AKIRIN2, DLGAP5, and NSFL1C in PC we aim to improve the understanding of how hereditary factors modulate susceptibility to aggressive PC.