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Expression of tight-junction protein claudin-7 is an early event in gastric tumorigenesis

Adam H Johnson1, Henry F Frierson, Alexander Zaika

  • 1Digestive Health Center of Excellence, University of Virginia Health System, P.O. Box 800708, Charlottesville, VA 22908-0708, USA.

The American Journal of Pathology
|July 29, 2005
PubMed

Insights

Trefoil factor-1 (Tff1) down-regulation in gastric cancer prompts investigation into Tff1 knockout mice. Claudin-7 (CLDN7) overexpression in mouse gastric dysplasia suggests its role in early gastric tumorigenesis.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Oncology

Background:

  • Trefoil factor-1 (Tff1) is significantly downregulated in human gastric cancers.
  • Tff1 knockout mouse models offer a platform to study early molecular changes in gastric preneoplasia.

Purpose of the Study:

  • To identify molecular alterations associated with preneoplastic gastric dysplasia in Tff1 knockout mice.
  • To investigate the role of Claudin-7 (CLDN7) in gastric tumorigenesis.

Main Methods:

  • Oligonucleotide microarray gene expression analysis comparing Tff1-/- mice gastric dysplasia to wild-type mice gastric mucosa.
  • Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) for gene validation.
  • Comparison of gene expression data with human gastric cancer databases.

Main Results:

  • Claudin-7 (CLDN7), Early Growth Response-1 (EGR1), and Epithelial Membrane Protein-1 (EMP1) were significantly overexpressed in Tff1-/- mouse gastric dysplasia.
  • CLDN7 was consistently overexpressed in Tff1-/- gastric dysplasia and human gastric adenocarcinoma samples.
  • CLDN7 expression increased with gastric lesion progression (metaplasia, dysplasia, adenocarcinoma) and was prevalent in intestinal-type gastric adenocarcinomas.

Conclusions:

  • CLDN7 overexpression is an early event in gastric tumorigenesis, potentially driven by Tff1 downregulation.
  • CLDN7 serves as a potential biomarker for gastric dysplasia and intestinal-type gastric adenocarcinoma.

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