Since Raptor is the unique and functional component of mTORC1, we performed Cre/LoxP mediated Raptor knockout by hydrodynamic tranfection in Raptorfl/fl mice. The study design is similar to what we have published previously . In brief, either pT3-EF1a (pT3, empty vector control) or pT3-EF1a-Cre (Cre) plasmid was co-injected with YAPS127A and ΔN90-β-catenin plasmids into Raptorfl/fl mice (Figure 3A). Mice were monitored and sacrificed when they were moribund or 21.3 weeks post injection. All the pT3 treated mice developed a lethal burden of liver tumors by 12.3 weeks post injection and were euthanized. In striking contrast, all Cre injected mice remained healthy until 21.3 weeks post injection (Figure 3B and Table 1). Upon dissection, within 10 to 12 weeks post injection, all pT3 injected mice showed massive liver tumors with high liver weight as well as liver/body ratio (Figure 3C and 3D). Histologically, tumor cells resembled fetal or crowded fetal subtype of human HB, characterized by small cell size as well as small round or oval nuclei . Tumor cells were highly proliferative, as indicated by Ki67 staining. At this time point, all Cre injected mice showed the absence of tumor lesions on the liver surface, with normal liver weight and liver/body ratio (Figure 3C and 3D). Histological examination revealed that the liver of Cre injected mice was completely normal with no microscopic lesions (Figure 3D). At 15 to 21 weeks post injection, small tumor nodules could be found in Cre injected mouse livers (Figure 3D). Histologically, tumors were exclusively HB, with frequent Ki67 positive cells (Figure 3D).