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

Cancer Cell. 2002 Mar;1(2):145-55. doi: 10.1016/s1535-6108(02)00035-1.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Mutation / genetics
  • Neoplasms / metabolism*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • TCF Transcription Factors
  • Trans-Activators / metabolism*
  • Transcription Factor 4
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, human
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Tcf4 protein, rat
  • Tcf7l2 protein, rat
  • Trans-Activators
  • Transcription Factor 4
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin