Increased beta-catenin mRNA levels and mutational alterations of the APC and beta-catenin gene are present in intestinal-type gastric cancer

Carcinogenesis. 2002 Jan;23(1):87-91. doi: 10.1093/carcin/23.1.87.

Abstract

Beta-catenin is critical for intercellular adhesion and also plays a role as a transcription activating protein in the Wnt signalling pathway. Increased protein levels and mutation of the beta-catenin gene have been demonstrated in various cancers; however, the role of beta-catenin in gastric cancer remains largely unknown. Using gastric cancer tissues and normal adjacent gastric mucosa obtained from 20 patients with gastric cancer (eight diffuse-type, 12 intestinal-type) undergoing gastric resection or endoscopy, we assessed the expression of beta-catenin by immunohistochemistry and quantitative PCR analysis. Furthermore, the tumour suppressor gene APC, which down-regulates the beta-catenin levels was analysed for mutations. Overall mRNA levels of beta-catenin were significantly increased in the tumour samples compared with the matched normal gastric mucosa (P < 0.05). Increased beta-catenin mRNA levels were significantly more frequent in intestinal-type gastric cancers as compared to diffuse-type gastric cancers (P < 0.01). Six out of 20 tumours exhibited >6-fold increased beta-catenin mRNA levels as compared with normal mucosa. APC gene mutations were found in four cases. A beta-catenin gene mutation was identified only in one intestinal-type gastric cancer exhibiting a massive overexpression of beta-catenin mRNA in the tumour. In intestinal-type gastric cancers beta-catenin mRNA levels are greatly enhanced. APC and beta-catenin gene mutations are also present primarily in intestinal-type gastric cancers. These findings support the hypothesis that in intestinal-type gastric cancers the accumulation of beta-catenin protein may result from impaired degradation of the beta-catenin protein due to alterations of the beta-catenin and APC genes, as well as from enhanced beta-catenin transcription which is present in the great majority of intestinal-type gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA Mutational Analysis
  • Female
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Genes, APC*
  • Helicobacter Infections / genetics
  • Helicobacter Infections / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymorphism, Single-Stranded Conformational
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Trans-Activators*
  • beta Catenin

Substances

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