A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer Academic Article uri icon

Overview

MeSH Major

  • Carcinoma, Hepatocellular
  • DNA Mutational Analysis
  • Genes, Tumor Suppressor
  • Liver Neoplasms
  • Nuclear Receptor Coactivator 2
  • Transposases

abstract

  • The Sleeping Beauty (SB) transposon mutagenesis system is a powerful tool that facilitates the discovery of mutations that accelerate tumorigenesis. In this study, we sought to identify mutations that cooperate with MYC, one of the most commonly dysregulated genes in human malignancy. We performed a forward genetic screen with a mouse model of MYC-induced liver cancer using SB-mediated mutagenesis. We sequenced insertions in 63 liver tumor nodules and identified at least 16 genes/loci that contribute to accelerated tumor development. RNAi-mediated knockdown in a liver progenitor cell line further validate three of these genes, Ncoa2/Src-2, Zfx, and Dtnb, as tumor suppressors in liver cancer. Moreover, deletion of Ncoa2/Src-2 in mice predisposes to diethylnitrosamine-induced liver tumorigenesis. These findings reveal genes and pathways that functionally restrain MYC-mediated liver tumorigenesis and therefore may provide targets for cancer therapy.

publication date

  • May 22, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3361419

Digital Object Identifier (DOI)

  • 10.1073/pnas.1115433109

PubMed ID

  • 22556267

Additional Document Info

start page

  • E1377

end page

  • 86

volume

  • 109

number

  • 21