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

β-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 β-catenin gene have been demonstrated in various cancers; however, the role of β-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 β-catenin by immunohistochemistry and quantitative PCR analysis. Furthermore, the tumour suppressor gene APC, which down-regulates the β-catenin levels was analysed for mutations. Overall mRNA levels of β-catenin were significantly increased in the tumour samples compared with the matched normal gastric mucosa (P 6-fold increased β-catenin mRNA levels as compared with normal mucosa. APC gene mutations were found in four cases. A β-catenin gene mutation was identified only in one intestinal-type gastric cancer exhibiting a massive overexpression of β-catenin mRNA in the tumour. In intestinal-type gastric cancers βcatenin mRNA levels are greatly enhanced. APC and β-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 β-catenin protein may result from impaired degradation of the β-catenin protein due to alterations of the β-catenin and APC genes, as well as from enhanced βcatenin transcription which is present in the great majority of intestinal-type gastric cancers.