Abstract 1109: Characterization of hepatoma-derived growth factor (HDGF) as a novel survival related protein in prostate cancer cells

Abstract

Abstract Prostate cancer (PCa) is a leading cause of death by cancer in men, resulting in approximately 32,000 deaths each year. While the cause of PCa is not clearly known at this time, some risk factors include age, diet, race, and activation of certain oncogenes. Hepatoma-derived growth factor (HDGF) is a recently discovered oncogene and a key mitogenic growth factor which is activated in lung, liver, and skin cancers, however, its role in the development of PCa is unknown. Therefore, the goal of this study is to characterize the role of HDGF in prostate carcinogenesis. A normal prostate cell line, RWPE-1, and four different PCa cell lines, LNCaP, 22RV1, DU145, and PC-3, were analyzed for their expression level of HDGF by western blot analysis. Results of this evaluation revealed that HDGF is over-expressed in multiple PCa cell lines while minimally expressed in RWPE-1 cells. When the HDGF gene is ectopically over-expressed in normal RWPE-1 cells, proliferative rate was increased by 1.5 fold compared to the normal cells, suggesting that HDGF has growth stimulating activity. On the contrary, down regulation of HDGF expression by siRNA significantly inhibited the survival of both androgen dependent (LNCaP) and androgen independent (PC-3) PCa cells. DNA content analysis of RWPE-1 cells stably expressing HDGF by flow cytometry showed that the majority of the cells were in the G2/M phase (55%) of the cell cycle while only 28% of the control RWPE-1 cells were at G2/M phase implying HDGF may have a mitotic function in prostate cells. Furthermore, AKT (phosphorylated form) and NFκB (p65 domain) signaling molecules were found to be activated in RWPE-1 cells expressing HDGF. This activation resulted in the increase of anti-apoptotic molecules Cyclin-E and BCL-2 and the simultaneous decrease in the pro-apoptotic molecule Bax. Activation of AKT-NFκB pathway plays a vital role in the carcinogenesis of several cancers, including PCa. Thus, HDGF over-expression may play a role in regulating this survival pathway in prostate carcinogenesis. Collectively, the results of this study suggest that HDGF is a key player in the development of PCa and may serve as a target for chemopreventive or chemotherapeutic strategies in PCa. 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 1109. doi:10.1158/1538-7445.AM2011-1109