Fig. 5.

Liver lesions developed in AKT/TAZ mice display activation of Hippo and AKT/mTOR pathways. (A) Representative immunohistochemical patterns of a cholangiocellular tumor exhibiting immunoreactivity for HA-Tag(AKT) and nuclear TAZ, as well as for downstream effectors of the Hippo (NOTCH1, NOTCH2, and JAG1) and AKT/mTOR (phosphorylated/activated AKT or p-AKT; phosphorylated/inactivated GSK-3β or p-GSK-3β; and phosphorylated/activated RPS6 or p-RPS6) pathways. Original magnification: 200x; scale bar: 100 μm. (B) Upregulation of the Hippo pathway targets CCN1, CCN2, and NOTCH2 in AKT/TAZ livers (10 weeks post-injection) compared with livers injected with the empty vector (Vector), as assessed by quantitative real-time RT-PCR. Abbreviations: H&E, hematoxylin and eosin staining; ST, non-tumorous surrounding tissue; T, tumor. Data are expressed as means ± SD. ***p < 0.0001 and **p < 0.01 vs. empty vector-injected mice