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Effects of Helicobacter pylori on the cadherin–catenin complex
  1. J R Bebb1,
  2. L Leach2,
  3. A Zaitoun3,
  4. N Hand3,
  5. D P Letley1,
  6. R Thomas1,
  7. J C Atherton1
  1. 1Wolfson Centre for Digestive Diseases and Institute of Infections, Inflammation and Immunity, University Hospital Nottingham, Nottingham, UK
  2. 2Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University Hospital Nottingham
  3. 3Department of Histopathology, University Hospital Nottingham
  1. Correspondence to:
 J R Bebb
 Wolfson Centre for Digestive Diseases, University Hospital, Nottingham, NG7 2UH; jamesbebb{at}doctors.org.uk

Abstract

Background: The cadherin–catenin complex is the key component of the adherens junction in epithelial cells, and changes in this complex are implicated in gastric adenocarcinoma. Germline mutations in E-cadherin have been described in diffuse-type gastric adenocarcinoma. Helicobacter pylori infection is the first stage in gastric carcinogenesis.

Aims: To determine whether H pylori was associated with changes in the complex, and whether this was affected by virulence of the strain.

Methods: Epithelial cell lines were cultured with H pylori using the wild-type pathogenic and non-pathogenic strains and CagE null and VacA null isogenic mutants. Gastric biopsy specimens at endoscopy were obtained from patients with (n = 17) and without (n = 15) H pylori infection, and E-cadherin and β–catenin expression was assessed by immunohistochemistry. H pylori was typed by polymerase chain reaction from these patients for CagE and VacA.

Results: In vitro studies showed that coculture with a pathogenic strain of H pylori led to disruption of epithelial junctional β-catenin expression, but without evidence of nuclear translocation or signalling. This effect was independent of a functional Cag pathogenicity island and vacuolating activity, but dependent on live bacteria. No marked differences in β-catenin or E-cadherin expression were seen in gastric biopsy specimens in patients with and without H pylori infection.

Conclusion: Acute H pylori infection disrupts junctional β-catenin in vitro, but chronic infection by H pylori has no effect on E-cadherin and β-catenin expression, as seen in gastric biopsy specimens at the initial gastritis stage of the proposed Correa pathway of gastric carcinogenesis. A later effect at the later stages of atrophy or intestinal metaplasia cannot be ruled out.

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Footnotes

  • Published Online First 5 May 2006

  • Funding: JRB was supported by Fellowships from The Wellcome Trust (Entry Level) and the Medical Research Council (Clinical Training Fellowship). JCA holds a Senior Clinical Fellowship from the Medical Research Council.

  • Competing interests: None declared.

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