Altered expression and mutation of beta-catenin gene in gastric carcinomas and cell lines

Int J Cancer. 2001 Mar 20;95(2):108-13. doi: 10.1002/1097-0215(20010320)95:2<108::aid-ijc1019>;2-#.


beta-catenin serves not only as a structural component of the E-cadherin-mediated cell-cell adhesion system, but also as a signaling molecule of the Wnt/wingless pathway. Deregulated expression of beta-catenin and mutations of the gene have been identified in a number of human malignancies. To determine the role of beta-catenin defects in stomach cancer, we investigated beta-catenin exon 3 mutations and altered protein expression in 77 primary gastric carcinomas and 11 cell lines. In addition, the immunohistochemical expression pattern of beta-catenin in 303 consecutive gastric cancers was determined and their relationships with clinicopathologic features and patient outcome were investigated. This study revealed 5% (4 of 77) tumors and 27% (3 of 11) cell lines with beta-catenin gene alteration, 6 missense mutations, and 1 interstitial deletion. These genetic changes were shown to correlate closely with nuclear localization of the protein (p = 0.001). In an immunohistochemical analysis, abnormal expressions of beta-catenin, such as nuclear accumulation and loss of membranous distribution, were detected in 27% (81 of 303) of tumors overall. These altered beta-catenin expressions were more commonly observed in 37% (58 of 158) diffuse type gastric carcinomas (p < 0.001). Loss of membranous beta-catenin staining was associated with poor survival (p = 0.045). In conclusion, our results demonstrate that beta-catenin mutations are common in gastric cancer cell lines but occur infrequently in gastric carcinoma tissues. These mutations are one of the causes of the nuclear accumulation of beta-catenin. Frequent abnormalities of beta-catenin expression in gastric carcinoma support the idea that both structural and signaling functions of the protein play a critical role in gastric carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / biosynthesis*
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Exons
  • Female
  • Follow-Up Studies
  • Gastric Mucosa / metabolism
  • Gene Deletion
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation*
  • Mutation, Missense
  • Point Mutation
  • Sex Factors
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Time Factors
  • Trans-Activators*
  • Treatment Outcome
  • Tumor Cells, Cultured
  • beta Catenin


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