Fig. 1.

Overexpression of constitutively activated TAZ (TAZS89A) rarely induces intrahepatic cholangiocarcinoma development in mice. (A) Scheme of the experiments conducted. Specifically, FVB/N mice were hydrodynamically injected with the empty vector (Vector; n=10) or an activated form of TAZ (TAZS89A; n=40). Five empty vector-injected mice, and 15 TAZS89A-injected mice were sacrificed 10 weeks post-injection, whereas 5 empty vector-injected and 25 TAZS89A-injected mice were killed 40 weeks post-injection. (B,C) Macroscopic images of empty vector- (B) and TAZS89A-injected (C) mouse livers at 10 weeks post-injection showing a normal appearance. (D) Development of a single tumor in a TAZS89A-injected mouse sacrificed 10 weeks post-injection. (E) Large tumor developed in a TAZS89A-injected mouse sacrificed 40 weeks post-injection. Tumors depicted in (D) and (E) exhibited histological features of intrahepatic cholangiocarcinomas, with cancer cells organized in tubular and pseudoglandular structures surrounded by desmoplastic stroma. In addition, the lesions displayed robust immunoreactivity for cytokeratin (CK) 7 and 19, two biliary markers, further corroborating their cholangiocellular differentiation. In addition, the same lesions were characterized by pronounced nuclear immunoreactivity for TAZ protein. Furthermore, the lesions exhibited remarkable positiveness for activated/phosphorylated (p-)Akt: Original magnification: 40x, 100x, and 200x, as indicated in the pictures. Scale bars are indicated in the pictures. Abbreviations: H&E, hematoxylin and eosin staining; w.p.i, weeks post-injection