Role of C-JUN terminal kinases (JNK1/2) in the development of cancer of the biliary tract

Cholangiocarcinoma (CCA) is an aggressive malignant bile duct cancer, and the second most common primary liver tumor In Europe, around 13,000 new CCA cases were diagnosed per year. However, the pathogenesis of CCA remains elusive and lack of diagnostic as well as treatment tools impede a better outcome for patients. In the present study, we use a new animal model of CCA, to understand the molecular mechanism. In the present work, we hypothesize that the synergistic dysfunction of Jnk1 and Jnk2 in hepatocytes drives the development of cholangiocarcinogenesis. Mice with specific deletion of Jnk1/2 in hepatocytes (JnkΔhepa) and floxed (Jnkf/f) control mice were sacrificed at different time points during liver disease progression. Likewise, different toxicity treatments (i.e., TAA, DEN/TAA and DEN/CCl4) and experimental models were used...