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c-Myc-driven Hepatocarcinogenesis

2021; International Institute of Anticancer Research (IIAR) Conferences 1997. Athens, Greece. Abstracts; Volume: 41; Issue: 10 Linguagem: Inglês

10.21873/anticanres.15307

1791-7530

Hyuk Moon, Hyun-Jung Park, Simon Weonsang Ro,

Cancer-related gene regulation

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 G12V ), β-catenin (β-catenin S33Y ), 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 S33Y 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 T58A , minimizing the role of the mutation in hepatocarcinogenesis.