Aims: Liver cancer is a major health concern worldwide, ranking the second among cancer-related mortality. The c-Myc gene is epigenetically altered in almost 50% of human liver cancers, leading to persistent over-expression of c-Myc. Mutation at codon...
Aims: Liver cancer is a major health concern worldwide, ranking the second among cancer-related mortality. The c-Myc gene is epigenetically altered in almost 50% of human liver cancers, leading to persistent over-expression of c-Myc. Mutation at codon 58 of c-Myc (c-Myc<sup>T58A</sup>) can enhance oncogenic potentials of c-Myc through suppressing apoptotic signaling cascades or stabilizing the oncoprotein. In this study, we compared tumorigenic potentials between c-Myc<sup>T58A</sup> and the wild-type (WT) c-Myc in the liver.
Methods: Transgenic mouse models expressing c-Myc<sup>T58A</sup> and WT c-Myc were developed using hydrodynamic transfection. Transposons encoding an activated from of human H-RAS were mixed with transposons encoding either c-Myc<sup>T58A</sup> or WT c-Myc. The DNA mixtures were injected into the lateral tail veins of 6-week-old C57BL/6 mice. Mice were monitored at least twice per week and sacrificed when moribund. Tumor-bearing livers were formalin fixed for hematoxylin- eosin staining and immunohistochemistry.
Results: Hepatocellular carcinomas (HCC) were induced by co- expression of HRAS with either c-Myc<sup>T58A</sup> or WT c-Myc with 100% penetration. There was no significant difference in animal survivals between the c-Myc<sup>T58A</sup> and WT c-Myc groups. The numbers and sizes of tumors were similar between the two groups. Cellular proliferation (determined by Ki-67 staining) and apoptosis levels (by TUNEL assay) were also similar between c-Myc<sup>T58A</sup> and WT c-Myc groups. Finally, there was no difference in phenotypes of malignant hepatocytes between the two groups.
Conclusions: T58A mutation does not enhance tumorigenic potentials of c-MYC in our transgenic mouse models. No downregulation of apoptosis was detected in c-Myc<sup>T58A</sup>, compared with WT c-Myc.