Volume 42, Issue 6, Pages 842-849 (June 2005) Activation of the canonical Wnt/β-catenin pathway confers growth advantages in c- Myc/E2F1 transgenic mouse model of liver cancer  Diego F. Calvisi, Elizabeth A. Conner, Sara Ladu, Eric R. Lemmer, Valentina M. Factor, Snorri S. Thorgeirsson  Journal of Hepatology  Volume 42, Issue 6, Pages 842-849 (June 2005) DOI: 10.1016/j.jhep.2005.01.029 Copyright © 2005 Terms and Conditions

Fig. 1 Acceleration of liver cancer in c-Myc/E2F1 double transgenic mice. (A–C) Incidence and time course of hepatic lesions in c-Myc, E2F1 and c-Myc/E2F1 transgenic mice. (D–F) Morphology of hepatic lesions at 6 months of age; (D) Dysplastic liver from c-Myc mouse. (E) Focus composed of small cells directly adjacent to a portal tract (arrows), and large dysplastic cells surrounding a central vein from E2F1 mouse. (F) Hepatocellular carcinoma, trabecular pattern (arrow) from c-Myc/E2F1 mouse. pt, portal tract; cv, central vein. Original magnification, ×200. Journal of Hepatology 2005 42, 842-849DOI: (10.1016/j.jhep.2005.01.029) Copyright © 2005 Terms and Conditions

Fig. 2 Representative Western blot analysis showing the expression of β-catenin (A), GSK-3β complex members (B), canonical Wnt cascade members (C), and β-catenin target genes (D). n, nuclear levels; t, total levels; p, phosphorylated; wt, wild-type liver. HCCs (T1–3) with β-catenin activation; HCC (T4–6) without β-catenin activation. Journal of Hepatology 2005 42, 842-849DOI: (10.1016/j.jhep.2005.01.029) Copyright © 2005 Terms and Conditions

Fig. 3 Summary of findings regarding the status of β-catenin, GSK-β complex, Wnt-1 cascade, and β-catenin target genes detected by DNA sequencing, microsatellite and Western blot analysis in c-Myc/E2F1 HCCs. Journal of Hepatology 2005 42, 842-849DOI: (10.1016/j.jhep.2005.01.029) Copyright © 2005 Terms and Conditions

Fig. 4 Microsatellite analysis of the Axin locus using the polymorphic markers D17Mit55 (A) and D17Mit100 (B). Wt, wild-type liver; lanes 1,2 HCCs with nuclear β-catenin; lanes 3,4 without nuclear β-catenin. Journal of Hepatology 2005 42, 842-849DOI: (10.1016/j.jhep.2005.01.029) Copyright © 2005 Terms and Conditions

Fig. 5 Effect of β-catenin activation on tumor growth in c-Myc (19 months of age) and c-Myc/E2F1 (12 months of age) HCCs. (A) PCNA labeling index; (B) Apoptotic index; (C) growth rate; (D) tumor size. Each bar represents the mean+SEM, n=6–12. Journal of Hepatology 2005 42, 842-849DOI: (10.1016/j.jhep.2005.01.029) Copyright © 2005 Terms and Conditions