Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer

Nat Genet. 2001 May;28(1):53-7. doi: 10.1038/ng0501-53.


Constitutive activation of the Wnt signaling pathway is a root cause of many colon cancers. Activation of this pathway is caused by genetic mutations that stabilize the beta-catenin protein, allowing it to accumulate in the nucleus and form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of transcription factors (referred to collectively as LEF/TCFs) to activate transcription of target genes. Target genes such as MYC, CCND1, MMP7 and TCF7 (refs. 5-9) are normally expressed in colon tissue, so it has been proposed that abnormal expression levels or patterns imposed by beta-catenin/TCF complexes have a role in tumor progression. We report here that LEF1 is a new type of target gene ectopically activated in colon cancer. The pattern of this ectopic expression is unusual because it derives from selective activation of a promoter for a full-length LEF1 isoform that binds beta-catenin, but not a second, intronic promoter that drives expression of a dominant-negative isoform. beta-catenin/TCF complexes can activate the promoter for full-length LEF1, indicating that in cancer high levels of these complexes misregulate transcription to favor a positive feedback loop for Wnt signaling by inducing selective expression of full-length, beta-catenin-sensitive forms of LEF/TCFs.

Publication types

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

MeSH terms

  • Colonic Neoplasms / genetics*
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Introns
  • Lymphoid Enhancer-Binding Factor 1
  • Molecular Sequence Data
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction
  • T Cell Transcription Factor 1
  • Trans-Activators*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Neoplasm Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • T Cell Transcription Factor 1
  • TCF7 protein, human
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin

Associated data

  • GENBANK/AF288570
  • GENBANK/AF288571