ZFIN ID: ZDB-PUB-121016-5
An inducible Myc zebrafish liver tumor model revealed conserved Myc signatures with mammalian liver tumors
Li, Z., Zheng, W., Wang, Z., Zeng, Z., Zhan, H., Li, C., Zhou, L., Yan, C., Spitsbergen, J.M., and Gong, Z.
Date: 2013
Source: Disease models & mechanisms 427(1): 223-226 (Journal)
Registered Authors: Gong, Zhiyuan, Li, Zhen, Spitsbergen, Jan, Zhou, Li
Keywords: none
Microarrays: GEO:GSE40745
MeSH Terms: Animals; Animals, Genetically Modified; Carcinoma, Hepatocellular/genetics; Carcinoma, Hepatocellular/pathology; Disease Models, Animal (all 25) expand
PubMed: 23038063 Full text @ Dis. Model. Mech.
FIGURES   (current status)
ABSTRACT

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.

ADDITIONAL INFORMATION