Cell Cycle Regulation and Hepatocarcinogenesis

Hepatocellular carcinoma (HCC) develops on a background of chronic hepatitis or cirrhosis. The slow progression of this disease has facilitated the identification of discrete pathologic stages. Increased rates of hepatocyte proliferation in preneoplastic nodules is an early event in the progression of HCC. Increased cell turnover results in the selection of monoclonal hepatocyte populations that subsequently undergo genomic alterations that lead to the development of HCC. The heterogeneous nature of genomic alterations identified in tumors from patients with HCC has impeded the identification of regulatory pathways whose disruption are critical for tumor initiation. However, several regulatory networks important for liver cell proliferation have been characterized using the partial hepatectomy model, an in vivo model of liver cell cycle progression, and are likely relevant to the pathogenesis of hepatocellular carcinoma.