title: alpha-catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives.
abstract: OBJECTIVE
  The role of altered cell adhesion is critical for the development of epithelial cancers. E-cadherin plays an important role in the maintenance of cell-cell adhesion and its function is thought to be regulated by its associated cytoplasmic proteins, such as alpha-catenin and beta-catenin. To determine the role of alpha-catenin expression in gastric carcinogenesis, we studied its expression in human gastric cancer and in the gastric mucosa of first degree relatives with no clinical disease.
  
  
  METHODS
  alpha-Catenin expression was assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using gastric tissue specimens from patients with gastric cancer and from the gastric mucosa of first degree relatives of gastric cancer patients and healthy controls.
  
  
  RESULTS
  mRNA levels of alpha-catenin were reduced or absent in 13 of 19 gastric cancer tissues, which differed significantly from levels found in the tumour free gastric mucosa of cancer patients (p<0.05). Of the cancer samples with altered alpha-catenin mRNA levels, alpha-catenin expression was negative in seven and decreased in six cases. Interestingly, decreased alpha-catenin mRNA expression also occurred in the mucosa of the corpus (11/18) and antrum (4/18) of first degree relatives. In the corpus biopsies alpha-catenin expression was more often decreased or lost compared with the antrum biopsies in first degree relatives and healthy controls (p<0.05). Immunohistochemical analysis revealed membranous expression of alpha-catenin in gastric cancer cells and the non-malignant gastric epithelium. However, some cancers also exhibited loss of membranous staining. Generally, loss or downregulation of alpha-catenin mRNA in the gastric mucosa was associated with Helicobacter pylori infection (p<0.05).
  
  
  CONCLUSIONS
  Our findings suggest that loss or downregulation of alpha-catenin expression may be an early event in gastric carcinogenesis and may be associated with H pylori infection.
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, D-39120 Magdeburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: M P
authors.initials: MP
authors.lastname: Ebert
authors.forename: S
authors.initials: S
authors.lastname: Miehlke
authors.forename: H
authors.initials: H
authors.lastname: Rost
authors.forename: U
authors.initials: U
authors.lastname: Lendeckel
authors.forename: A
authors.initials: A
authors.lastname: Leodolter
authors.forename: M
authors.initials: M
authors.lastname: Stolte
authors.forename: E
authors.initials: E
authors.lastname: Bayerdörffer
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D005190:Family; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051178:alpha Catenin
chemical_list: C495273:CTNNA1 protein, human; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D051178:alpha Catenin