Akt/Notch activation drives rapid cholangiocarcinoma development originating from mature hepatocytes in the mouse

Introduction: Intrahepatic cholangiocarcinomas (ICCs) are primary liver tumors with a dismal prognosis. Activated AKT/mTOR pathway promotes both HCC and ICC development in the mouse liver. Notch signaling is known to play a critical role during bile duct development. Here we hypothesized that activated Notch signaling converted AKT-overexpressing preneoplastic hepatocytes into ICC in vivo. Methods: Activated Notch (NICD) alone or together with the activated form of AKT (myr-AKT) were stably transfected into the mouse liver via hydrodynamic injection. Dominant negative form of RBP-J (dnRBP-J) was co-injected with…