ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation.

Journal Article (Journal Article)

In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in beta-catenin lead to elevated beta-catenin levels, enhanced binding of beta-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by beta-catenin or ligand-induced activation of a beta-catenin-estrogen receptor fusion protein. Human cancers with beta-catenin regulatory defects had elevated ITF-2 expression, and ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note, ITF-2 promoted neoplastic transformation of RK3E cells. We propose that ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in beta-catenin regulation.

Full Text

Duke Authors

Cited Authors

  • Kolligs, FT; Nieman, MT; Winer, I; Hu, G; Van Mater, D; Feng, Y; Smith, IM; Wu, R; Zhai, Y; Cho, KR; Fearon, ER

Published Date

  • March 2002

Published In

Volume / Issue

  • 1 / 2

Start / End Page

  • 145 - 155

PubMed ID

  • 12086873

International Standard Serial Number (ISSN)

  • 1535-6108

Digital Object Identifier (DOI)

  • 10.1016/s1535-6108(02)00035-1


  • eng

Conference Location

  • United States