Deletion of cyclin E1 inhibits DEN induced hepatocarcinogenesis in mice

Transition of resting cells into the proliferative state of the cell cycle is associated with strong expression of E-type cyclins potentially contributing to early tumorigenesis. The aim of this study was to characterize constitutive cyclin E1 (CcnE1-/-) and cyclin E2 (CcnE2-/-) knockout mice in a model of chemically induced hepatocarcinogenesis. Single injection of the carcinogen diethyl-nitrosamine (DEN, 25mg/kg) was applied to CcnE1-/-, CcnE2-/- and wild-type (WT) animals at the age of 14 days to induce hepatocellular carcinoma (HCC). In addition, 6–8 weeks old WT, CcnE1-/- and CcnE2-/- mice were treated once with 200mg/kg DEN and analyzed from 0h up to 240h after injection for early tumorigenic effects.