c-Myc-driven Hepatocarcinogenesis.

BACKGROUND/AIM: Dysregulation of the c-Myc gene is frequently found in human hepatocellular carcinoma (HCC), often accompanied by genetic and epigenetic alterations in other cancer-related genes. Here, we investigated the tumorigenic potential of c-Myc in diverse genetic environments in which the Ras, Wnt/β-catenin, Sonic hedgehog, or P53 pathways were either activated or inactivated.

MATERIALS AND METHODS

Hydrodynamic tail vein injection was employed to administer expression transposons and generate transgenic livers expressing c-Myc together with a constitutively active form of RAS (HRAS), β-catenin (β-catenin), Smo (SmoM2), or short hairpin RNA targeting P53 (shp53).

RESULTS

c-Myc was most tumorigenic when the RAS signaling pathway was activated, whereas no tumors were found in mice when either β-catenin or SmoM2 was co-expressed with c-Myc. Approximately 40% of mice had HCC when c-Myc was over-expressed under P53 inactivation. Furthermore, we investigated the effect of mutation in c-Myc on hepatocarcinogenesis.

CONCLUSION

No significant differences in tumorigenic potential were found between wild type c-Myc and c-Myc, minimizing the role of the mutation in hepatocarcinogenesis.