Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma

J Cancer Res Clin Oncol. 2005 Dec;131(12):773-82. doi: 10.1007/s00432-005-0027-y. Epub 2005 Nov 15.


Purpose: The Wnt pathway is involved in carcinogenesis and three regulatory genes of the Wnt pathway, APC, beta-catenin and Axin are mutated in some primary human cancers. Mutations in these genes can impair the down regulation of beta-catenin, which results in the stabilization of beta-catenin, accumulation of free beta-catenin and subsequent activation of the Wnt pathway. To clarify the genetic alterations of components of the Wnt pathway in oral squamous cell carcinoma (SCC), we examined mutations in the APC, beta-catenin and Axin genes and subcellular localization of beta-catenin.

Methods: 20 oral SCC tissues and four cell lines derived from oral SCC were used. Mutational analysis was performed by a single-strand conformation polymorphism (SSCP) method and direct sequencing analysis. The samples were also examined by immunohistochemical staining and immunoblot analysis.

Results: In 3 of 4 cell lines, mutations were observed in the APC and Axin1 genes without amino acid substitutions. In a clinical sample, a mutation in the Axin1 gene was detected; a T insertion at codon 250 resulted in the formation of a stop codon at codon 259. In addition, cytoplasmic accumulation of beta-catenin was observed in 3 (75%) of 4 cell lines and 18 (90%) of 20 cancer tissue samples.

Conclusion: The Axin1 gene may be one of the mutational target in oral SCC. In addition, the cytoplasmic accumulation of beta-catenin is a common characteristic of oral SCC, but is not closely associated with mutational alterations in the APC, beta-catenin and Axin1 genes.

MeSH terms

  • Axin Protein
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cytoplasm / metabolism*
  • DNA, Neoplasm / analysis
  • Fluorescent Antibody Technique, Direct
  • Genes, APC*
  • Humans
  • Immunohistochemistry
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Repressor Proteins / genetics*
  • Sequence Analysis, DNA
  • Signal Transduction / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • AXIN1 protein, human
  • Axin Protein
  • CTNNB1 protein, human
  • DNA, Neoplasm
  • Repressor Proteins
  • beta Catenin