Fig. 8

Suppression of the canonical Notch signaling does not hinder liver carcinogenesis but suppresses the cholangiocellular differentiation of AKT/TAZ lesions. (A) Study design. Briefly, wild-type mice were subjected to hydrodynamic tail vein injection of either AKT/TAZ/pT3 (control) or AKT/TAZ/dnRBP-J plasmids. In particular, dnRBP-J is the dominant-negative form of the transcriptional coactivator recombination signal binding protein for immunoglobulin kJ region (RBP-J), whose overexpression effectively blunts the canonical Notch cascade. (B) Survival curve of AKT/TAZ/pT3 (control) and AKT/TAZ/dnRBP-J mice. Note that the survival of AKT/TAZ/dnRBP-J mice is only slightly longer than that of control mice. (C) Liver lesions from AKT/TAZ/dnRBP-J mice consist of pure trabecular and solid hepatocellular carcinomas. Due to their hepatocellular nature, the lesions exhibit positive immunoreactivity for HNF4α and CPS1 hepatocellular markers. They are negative for the CK19 cholangiocellular marker. As expected, AKT/TAZ/dnRBP-J liver lesions express the HA-Tag(AKT), nuclear TAZ, and V5-Tag (dnRBP-J) proteins. Original magnifications: 40x and 200x; scale bar: 500 μm in 40x and 100 μm in 200x. Abbreviations: H&E, hematoxylin and eosin staining