Myc is a pleiotropic transcription factor that is involved in many cellular activities relevant to carcinogenesis including
hepatocarcinogenesis. The zebrafish has been increasingly used to model human diseases and it is particularly valuable to
help identify common and conserved molecular mechanisms in vertebrates. Here we generated a liver tumor model in transgenic
zebrafish by liver-specific expression of mouse Myc using a Tet-on system. Dosage-dependent induction of Myc expression specifically in the liver was observed in our Myc transgenic zebrafish, TO(Myc), and the elevated Myc expression caused liver hyperplasia which was progressed to hepatocellular adenoma and carcinoma with prolonged induction.
Next generation sequencing-based transcriptomic analyses indicated that ribosome proteins were overwhelmingly up-regulated
in the Myc-induced liver tumors. Cross species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human hepatocellular carcinoma. Finally,
we found that a small Myc target gene set of 16 genes that could be used to identify liver tumors due to Myc up-regulation.
Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species.