Cytoplasmic and nuclear accumulation of beta-catenin is rarely caused by CTNNB1 exon 3 mutations in cutaneous malignant melanoma

Int J Cancer. 2001 Jun 15;92(6):839-42. doi: 10.1002/ijc.1270.


Beta-catenin plays an important role in the Wnt signaling pathway by activating T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-regulated gene transcription. The level of beta-catenin is regulated through GSK-3beta phosphorylation of specific serine and threonine residues, all of which are encoded for in exon 3 of the beta-catenin gene (CTNNB1). Mutations altering the GSK-3beta phosphorylation sites lead to cellular accumulation of beta-catenin and constitutive transcription of Tcf/Lef target genes. Such mutations have previously been found in melanoma cell lines. In our study, primary melanomas and their corresponding metastases were screened for CTNNB1 exon 3 mutations using single-strand conformation polymorphism and nucleotide sequence analysis. One of 31 primary tumors and 1 of 37 metastases, both originating from the same patient, had a TCT to TTT mutation at codon 45, changing serine to phenylalanine. Immunohistochemical analysis revealed membranous localization of beta-catenin in a majority of the samples. The mutated primary tumor and metastasis, however, displayed widespread cytoplasmic and nuclear expression of beta-catenin. An additional 30% of the primary tumors showed focal cytoplasmic and nuclear staining. Thus, beta-catenin exon 3 mutations are rare in primary as well as metastatic melanomas and do not explain the abnormal cytoplasmic and nuclear localization of beta-catenin found in a relatively large fraction of primary melanomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism*
  • Codon
  • Cytoplasm / metabolism*
  • Cytoskeletal Proteins / biosynthesis*
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA Mutational Analysis
  • Exons
  • Humans
  • Immunohistochemistry
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Mutation
  • Phenylalanine / chemistry
  • Polymorphism, Single-Stranded Conformational
  • Sequence Analysis, DNA
  • Serine / chemistry
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Trans-Activators*
  • Transcription, Genetic
  • beta Catenin


  • CTNNB1 protein, human
  • Codon
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Serine
  • Phenylalanine