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The Zebrafish Model for Liver Carcinogenesis

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Molecular Genetics of Liver Neoplasia

Abstract

The zebrafish (Danio rerio) has been increasingly recognized as a promising animal model for cancer research. Zebrafish tumors can be generated by treatment with chemical carcinogens or by genetic approaches. The liver has been a main target organ for tumorigenesis after carcinogen treatment while many other tissue-specific tumors have been generated by tissue-specific expression of proven oncogenes. We have used both the chemical and transgenic approaches to generate liver tumors. By comparative analyses of transcriptome profiles between human liver tumors and carcinogen-induced zebrafish liver tumors, we have demonstrated a remarkable similarity in the molecular hallmarks during liver tumorigenesis between humans and zebrafish, thus validating the zebrafish model for human cancer studies. Recently, we have also generated stable transgenic zebrafish lines overexpressing the c-Myc and kras V12 in the liver using two different inducible gene expression systems. In both cases, we found that tumors can be reproducibly induced in the liver, and histopathological examination confirmed the production of liver neoplasia including heptocellular carcinoma. Thus, we have successfully established transgenic zebrafish models for liver cancers and these models will be further characterized in order to understand the molecular and genetic mechanisms of liver carcinogenesis as well as for anti-cancer drug discovery.

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Gong, Z. et al. (2010). The Zebrafish Model for Liver Carcinogenesis. In: Wang, X., Grisham, J., Thorgeirsson, S. (eds) Molecular Genetics of Liver Neoplasia. Cancer Genetics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6082-5_11

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