A transgenic zebrafish liver tumor model with inducible Myc expression reveals conserved Myc signatures with mammalian liver tumors

Li, Zhen, Zheng, Weiling, Wang, Zhengyuan, Zeng, Zhiqiang, Zhan, Huiqing, Li, Caixia, Zhou, Li, Yan, Chuan, Spitsbergen, Jan M, Gong, Zhiyuan (March 2013) A transgenic zebrafish liver tumor model with inducible Myc expression reveals conserved Myc signatures with mammalian liver tumors. DMM Disease Models and Mechanisms, 6 (2). pp. 414-423. ISSN 1754-8403

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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 in helping to 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 progressed to hepatocellular adenoma and carcinoma with prolonged induction. Next generation sequencing-based transcriptomic analyses indicated that ribosome proteins were overwhelmingly upregulated 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 those of hepatocellular carcinoma. Finally, we found that a small Myc target gene set of 16 genes could be used to identify liver tumors due to Myc upregulation. Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > analysis and processing bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > neoplasms organism description > animal organism description > animal > fish bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types organs, tissues, organelles, cell types and functions > organs types and functions > liver diseases & disorders > cancer > cancer types > liver cancer organism description > animal > mammal organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types organism description > animal > fish > zebrafish
CSHL Authors:	Zhan, Huiqing
Communities:	CSHL labs > Zador lab CSHL labs > Zhan lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	March 2013
Date Deposited:	23 Jan 2024 16:39
Last Modified:	23 Jan 2024 16:39
PMCID:	PMC3597023
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41415

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