| First Author | Calvisi DF | Year | 2005 |
| Journal | J Hepatol | Volume | 42 |
| Issue | 6 | Pages | 842-9 |
| PubMed ID | 15885355 | Mgi Jnum | J:101128 |
| Mgi Id | MGI:3590626 | Doi | 10.1016/j.jhep.2005.01.029 |
| Citation | Calvisi DF, et al. (2005) Activation of the canonical Wnt/beta-catenin pathway confers growth advantages in c-Myc/E2F1 transgenic mouse model of liver cancer. J Hepatol 42(6):842-9 |
| abstractText | BACKGROUND/AIMS: Previously, we showed that activation of the beta-catenin/Wnt pathway is a dominant event during c-Myc/E2F1 hepatocarcinogenesis. Majority of c-Myc/E2F1 HCCs displayed nuclear accumulation of beta-catenin in the absence of beta-catenin mutations, suggesting that alterations in other members of the Wnt pathway might be responsible for nuclear localization of beta-catenin. Here, we investigated the mechanisms responsible for nuclear translocation of wild-type beta-catenin and addressed the potential contribution of the Wnt pathway in c-Myc/E2F1 hepatocarcinogenesis. METHODS: Status of the members of the Wnt pathway was determined through microsatellite and Western blot analysis. RESULTS: Majority of c-Myc/E2F1 HCCs exhibited multiple abnormalities in the Wnt pathway regardless of the presence of beta-catenin mutations. The observed abnormalities included overexpression of Wnt-1, Frizzled 1 and 2 receptors, Dishevelled-1, downregulation of Secreted frizzled-related protein-1, GSK-3beta inactivation, microsatellite instability at the Axin locus as well as induction of beta-catenin target genes, such as glutamine synthetase, glutamate transporter-1, and Wisp-1. HCCs with beta-catenin activation displayed significantly higher proliferation rate and larger tumor size when compared with beta-catenin negative tumors. CONCLUSIONS: The data demonstrate that multiple abnormalities in the members of the Wnt pathway lead to nuclear accumulation of beta-catenin and suggest that activation of Wnt pathway provides proliferative advantages in c-Myc/E2F1-driven hepatocarcinogenesis. |
