(A) Timeline of tumor development in AKT/Fbxw7ΔF mice (upper panel); macroscopy of AKT/Fbxw7ΔF livers (second panel); histopathologic features of the lesions (third panel); Ck19 immunostaining (fourth panel). (B) HA-tag immunohistochemistry showing cytoplasmic and nuclear staining for AKT and Fbxw7ΔF. The lesions are highly proliferative, as indicated by Ki67 nuclear immunoreactivity. (C) Western blotting of pathways activated in AKT/Fbxw7ΔF cholangiocellular lesions. Gapdh was used as a loading control. (D) mRNA levels of canonical Yap (Ctgf, Cyr61; upper panel) and Notch (Hey1, Nrarp; lower panel) target genes. (E) mRNA levels of c-Myc targets (Cdk4, Ccnd2, Skp2, Tert, Ldha, Ldhc, and Odc1). Scale bar: 200μm for 10×; 100μm for 20×. Abbreviations: H&E, hematoxylin and eosin staining; NL, normal liver; T, tumor; ns, not significant. * p <0.05; ** p <0.01; *** p <0.001.