Record Details
Myc-Induced Liver Tumors in Transgenic Zebrafish Can Regress in tp53 Null Mutation
ScholarsArchive at Oregon State University
| Field | Value |
|---|---|
| Title | Myc-Induced Liver Tumors in Transgenic Zebrafish Can Regress in tp53 Null Mutation |
| Names |
Sun, Lili
(creator) Anh Tuan Nguyen (creator) Spitsbergen, Jan M. (creator) Gong, Zhiyuan (creator) |
| Date Issued | 2015-01-22 (iso8601) |
| Note | This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Public Library of Science. The published article can be found at: http://www.plosone.org/. |
| Abstract | Hepatocellular carcinoma (HCC) is currently one of the top lethal cancers with an increasing trend. Deregulation of MYC in HCC is frequently detected and always correlated with poor prognosis. As the zebrafish genome contains two differentially expressed zebrafish myc orthologs, myca and mycb, it remains unclear about the oncogenicity of the two zebrafish myc genes. In the present study, we developed two transgenic zebrafish lines to overexpress myca and mycb respectively in the liver using a mifepristone-inducible system and found that both myc genes were oncogenic. Moreover, the transgenic expression of myca in hepatocytes caused robust liver tumors with several distinct phenotypes of variable severity. ~5% of myca transgenic fish developing multinodular HCC with cirrhosis after 8 months of induced myca expression. Apoptosis was also observed with myca expression; introduction of homozygous tp53[superscript -/-] mutation into the myca transgenic fish reduced apoptosis and accelerated tumor progression. The malignant status of hepatocytes was dependent on continued expression of myca; withdrawal of the mifepristone inducer resulted in a rapid regression of liver tumors, and the tumor regression occurred even in the tp53[superscript -/-] mutation background. Thus, our data demonstrated the robust oncogenicity of zebrafish myca and the requirement of sustained Myc overexpression for maintenance of the liver tumor phenotype in this transgenic model. Furthermore, tumor regression is independent of the function of Tp53. |
| Genre | Article |
| Access Condition | http://creativecommons.org/licenses/by/3.0/us/ |
| Identifier | Sun, L., Nguyen, A. T., Spitsbergen, J. M., & Gong, Z. (2015). Myc-Induced Liver Tumors in Transgenic Zebrafish Can Regress in tp53 Null Mutation. PLoS ONE, 10(1), e0117249. doi:10.1371/journal.pone.0117249 |
