Abstract 4164: HBx induced IGF-II expression is essential for hepatic dysplasia formation in mice

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC HCC is one of the most common cancers in the world. Chronic infection with HBV considered as a major risk factor. Among the four proteins from the HBV genome, HBx is a multifunctional regulatory protein which has been reported to be linked with hepatocellular carcinogenesis. We reported HBx induces liver cancer in transgenic mice. Among the multistep progress of liver carcinogenesis, enlargement (dysplasia) of the liver considered most critical point of this progression. HBx mice showed dysplasia within 4 weeks, dysplastic nodules and HCA after 6 months and HCC after 9 months of age. In this point we found out different expression pattern of IGF-II in HBx liver compare to wild type. In general this protein hormone predominantly active in fetal liver is strictly down-regulated shortly after birth. HBx mice have an increased liver/body weight ratio as well as cyclinD1 expression compared to wild type mice after 2 weeks. At that point, highly expressed IGF-II in wild mice started to decrease but in HBx mice the IGF-II expression still remained high level. The HBx-HepG2 cell line also has a higher expressed IGF-II level than the Mock-HepG2 cell line. Like in vivo data, the HBx cell line showed fast growth and increased cyclinD1 expression levels. Furthermore we found that abnormal cell growth was inhibited by neutralizing secreted IGF-II in vitro system with treatment of IGF-II antibody. In conclusion, we suggest IGF-II leads to liver dysfunction via over-proliferation of an HBx damaged hepatocyte. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4164.