In vivo RNAi screening identifies new mediators of p53 independent tumor suppressive functions of p19Arf in the liver

The sources of hepatocellular carcinoma are liver progenitor cells or hepatocytes. Interestingly, we observed differences between progenitor cell- and hepatocyte- derived hepatocellular carcinomas in mice. Oncogenic Nras (NrasG12V) efficiently triggers hepatocellular carcinomas derived from p53-/- liver progenitor cells, however almost no tumor growth is observed, when NrasG12V is delivered into p53-/- hepatocytes. Since aggressive hepatocellular carcinomas develop after short latency upon delivery of oncogenic Nras into p19Arf-/- hepatocytes, we suggest that p19Arf mediates a p53-independent tumor suppressive f…