BIR repeat-containing ubiquitin conjugating enzyme (BRUCE) regulation of β-catenin signaling in the progression of drug-induced hepatic fibrosis and carcinogenesis

Figure 1 Diethylnitrosamine-induced hepatic malignancy leads to earlier tumor initiation and an exacerbated patient hepatocellular carcinoma-like phenotype in BRUCE LKO mice. A: Diethylnitrosamine (DEN) model. Control and BRUCE LKO mice were treated with DEN over a time course schedule as indicated; B: Tumor onset in LKO mice happened after 8 mo post-DEN exposure, while tumor onset did not begin in control mice until 10-12 mo; C: Tumor in LKO mouse traced in red; D: After 14 mo of DEN exposure, control and LKO mice develop hepatocellular carcinoma; however, the LKO mice have a more exacerbated phenotype; E: Hematoxylin and Eosin staining reveals a trabecular histologic feature in LKO but not control; F: Timeline of key events of DEN-induced hepatic malignancy model. DEN: Diethylnitrosamine; LKO: Liver-specific knockout; HCC: Hepatocellular carcinoma; CTRL: Control; BRUCE: BIR repeat-containing ubiquitin conjugating enzyme.