Loss of Cyclin E1 attenuates hepatitis and hepatocarcinogenesis in a mouse model of chronic liver injury.

ABSTRACT: Chronic liver injury triggers liver fibrosis and hepatocellular carcinoma (HCC), the third leading cause of cancer-related mortality. Cyclin E1 (CcnE1, formerly designated Cyclin E) is a regulatory subunit of the Cyclin-dependent kinase 2 (CDK2). It is overexpressed in approximately 70% of human HCCs correlating with poor prognosis, while the relevance of its orthologue Cyclin E2 (CcnE2) is unclear. Hepatocyte-specific deletion of NF-kappa-B essential modulator (NEMO^Δhepa) leads to chronic hepatitis, liver fibrosis, and HCC as well as CcnE upregulation. To this end, we generated NEMO^Δhepa/CcnE1^-/- and NEMO^Δhepa/CcnE2^-/- double knockout mice and investigated age-dependent liver disease progression in these animals. Deletion of CcnE1 in

SUBMITTER: Ehedego H 

PROVIDER: S-EPMC6388396 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature