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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.