Inactivation of Itf2 promotes intestinal tumorigenesis in Apc(Min/+) mice

Biochem Biophys Res Commun. 2015 May 29;461(2):249-53. doi: 10.1016/j.bbrc.2015.04.009. Epub 2015 Apr 11.

Abstract

Deregulation of Wnt/β-catenin signaling following inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene is frequently found in colorectal cancer. We have previously shown that levels of ITF-2B, encoded by the β-catenin target gene ITF2 that is located on the tumor suppressor gene locus 18q21, are increased in colonic adenomas with deregulated β-catenin activity. However, during tumor progression ITF-2B levels are reduced, suggesting that ITF-2B interferes with tumor development. To investigate the role of ITF2 in intestinal tumorigenesis, we specifically inactivated Itf2 in the intestinal epithelium of Apc(Min/+) mice. We found that genetic disruption of Itf2 on the Apc(Min/+) background results in earlier death and a significant increase in tumor number and size in the small intestine. Based on these data Itf2 acts as a tumor suppressor gene of the intestinal tract that inhibits tumor initiation and growth.

Keywords: Apc(Min/+) mouse; ITF2; Intestinal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic*
  • Genes, APC*
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / pathology*
  • Intestine, Small / metabolism
  • Intestine, Small / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Transcription Factor 4

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Tcf4 protein, mouse
  • Transcription Factor 4