Fig. 3

Histopathologic characterization of liver lesions developed in AKT/TAZ mice. Two weeks post-injection, large and small altered cells, either alone or in small clusters, are easily detectable on the liver. Both cell types express HA-Tag(AKT) and nuclear TAZ, implying their origin from the injected plasmids. As expected, HA-Tag immunoreactivity is limited to the transfected cells, whereas faint cytoplasmic TAZ immunolabeling is appreciable in the unaffected hepatocytes. Of note, immunoreactivity for CK19, a biliary marker, is restricted to the small cell type and normal biliary cells. These small cells are also characterized by elevated proliferation, as indicated by positivity for Ki67 staining. Presumably, due to the different proliferation properties of the two altered cell types, the small cells rapidly replace the giant cells, forming CK19-positive tumors that occupy almost the whole liver by 10 weeks post-injection. Original magnification: 200x; scale bar: 100 μm