Organ size control is dominant over deregulation of the core cell cycle machinery to restrict hepatocyte proliferation in vivo

Introduction: The retinoblastoma (RB) tumor suppressor pathway is inactivated via genetic and epigenetic mechanisms in the large majority of human cancers, including hepatocellular carcinoma (HCC). Direct inhibition of RB pathway components by HBV and HCV viral proteins may also play an important role in HCC development following viral hepatitis. In mammals, RB family members (RB itself, p130, and p107) are the downstream mediators of the RB pathway and critical regulators of the G1/S transition of the cell cycle. Inactivation of the RB pathway by deletion of the three Rb family genes in the liver of adult mice…