p21 regulates liver progenitor cell activation and hepatocarcinogenesis in inflammation-associated liver disease

Introduction: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Given the poor prognosis in metastatic stage of the disease, new therapies are urgently needed. Previously it has been shown that loss of the cell-cycle regulator p21 dramatically accelerates hepatocarcinogenesis suggesting that p21 acts as tumor suppressor. In order to determine the impact of p21 in inflammation-induced carcinogenesis the Mdr2 mouse model was used. In Mdr2-/- mice, loss of the Abc4 protein leads to regurgitation of bile acids into the liver causing inflammation, fibrosis and tumor development. Methods: To ev…