Myc-Induced Liver Tumors in Transgenic Zebrafish Can Regress in tp53 Null Mutation Public Deposited

http://ir.library.oregonstate.edu/concern/articles/m326m372t

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/.

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • 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.
Resource Type
DOI
Date Available
Date Issued
Citation
  • 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
Series
Rights Statement
Funding Statement (additional comments about funding)
Publisher
Peer Reviewed
Language
Replaces
Additional Information
  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2015-03-10T20:00:45Z No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) SpitsbergenJanMicrobiologyMyc-InducedLiver.pdf: 9714144 bytes, checksum: 9625751c0d242e963db16f791c784720 (MD5) SpitsbergenJanMicrobiologyMyc-InducedLiver_SupportingInformation.zip: 9322399 bytes, checksum: 8deea7673b8a893f286777089d904f98 (MD5)
  • description.provenance : Made available in DSpace on 2015-03-10T20:01:02Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) SpitsbergenJanMicrobiologyMyc-InducedLiver.pdf: 9714144 bytes, checksum: 9625751c0d242e963db16f791c784720 (MD5) SpitsbergenJanMicrobiologyMyc-InducedLiver_SupportingInformation.zip: 9322399 bytes, checksum: 8deea7673b8a893f286777089d904f98 (MD5) Previous issue date: 2015-01-22
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2015-03-10T20:01:02Z (GMT) No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) SpitsbergenJanMicrobiologyMyc-InducedLiver.pdf: 9714144 bytes, checksum: 9625751c0d242e963db16f791c784720 (MD5) SpitsbergenJanMicrobiologyMyc-InducedLiver_SupportingInformation.zip: 9322399 bytes, checksum: 8deea7673b8a893f286777089d904f98 (MD5)

Relationships

Parents:

This work has no parents.

Last modified Default

Items