Interventional Gene Targeting Of Cell Cycle Regulators Identifies Cyclin E1 As A Suitable Target For Attenuating Hepatocellular Carcinoma Progression

Hepatocellular carcinoma (HCC) is one of the most severe tumor diseases with limited treatment options. Early and advanced stages of carcinogenesis are associated with sustained proliferation of hepatocytes and non-parenchymal cells (e.g. hepatic stellate cells, immune cells) regulated by Cyclins and Cyclin-dependent kinases (Cdks). E-Type Cyclins (E1, E2) and Cdk2 are involved in cell cycle re-entry of quiescent cells. Our previous unpublished work demonstrated that constitutive ablation of Cyclin E1 or Cdk2 in mice prevented HCC initiation. Therefore, in the present study we tested the hypothesis that Cyclin E1 or Cdk2 could be suitable targets for interventional HCC therapy.