Abstract

Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinoma (HCC), which is one of the male dominant diseases. Androgen signaling in liver may be related to carcinogenesis. In this study, we investigated whether HCV proteins cross-talk with androgen receptor (AR) signaling pathway for promotion of liver cancer. We have demonstrated that HCV core protein alone or in context with other HCV proteins enhances AR-mediated transcriptional activity, and further augments in the presence of androgen. Subsequent study suggested that HCV core protein activates STAT3, which in turn enhances AR-mediated transcription. This activity was blocked by a pharmacological inhibitor of Jak/Stat signaling pathway, AG490. Vascular endothelial growth factor (VEGF) is a target gene of androgen receptor in liver, and plays an important role in angiogenesis. Therefore, we examined whether HCV infection modulates VEGF expression in hepatocytes. Our results demonstrated that HCV enhances VEGF expression and facilitates tube formation in human coronary microvascular endothelial cells in the presence of AR. We are in the process of evaluating the AR targets in the hepatocytes following HCV infection.