Increased beta-catenin mRNA levels and mutational alterations of the APC and beta-catenin gene are present in intestinal-type gastric cancer.
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.
Ebert
Matthias P A
MP
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, D-39120 Magdeburg, Germany .
Fei
Guo
G
Kahmann
Sabine
S
Müller
Oliver
O
Yu
Jun
J
Sung
Joseph J Y
JJ
Malfertheiner
Peter
P
D000328:Adult; D000368:Aged; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D017491:Genes, APC; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin