Activation of the Notch signaling pathway is involved in the formation of cholangiocellular carcinomas

Throughout the last years the incidence of cholangiocellular carcinoma (CCC) in western european countries and the US is constantly rising. The pathogenesis of this devastating disease is however not well understood. Previously it was shown that the Notch signaling pathway is crucial for the development of the biliary system as loss of the Notch ligand Jagged results in hypoplasia of the biliary system (Alagille syndrome). Here we show that expression of the intracellular domain of the notch 1 receptor in transgenic mice leads to the formation of intrahepatic CCC. These tumors form highly aggressive carcinomas a…