FIGURE 8.

Graphic summary of action of Zhx2 in DEN‐induced HCC. The absence of Zhx2 completely blocks liver tumor formation 9 months after DEN treatment. Although DEN‐mediated DNA damage is the same in both Zhx2 ^KO and Zhx2 ^wt mice, hepatocyte proliferation, AKT2 activation, and IL‐6 expression are reduced in Zhx2 ^KO livers soon after DEN exposure. These data suggest that Zhx2 functions in both hepatocytes and nonparenchymal cells (NPCs)—a possibility that is supported by the fact that tumors are reduced, but not absent, in DEN‐treated Zhx2 ^Δliv mice.