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

Adam H. Johnson, Henry F. Frierson, Alexander Zaika, Steven M. Powell, James Roche, Sheila Crowe, Christopher A. Moskaluk, Wa'el El-Rifai

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Trefoil factor-1 (Tff1) expression is remarkably downregulated in nearly all human gastric cancers. Therefore, we used the Tff1 knockout mouse model to detect molecular changes in preneoplastic gastric dysplasia. Oligonucleotide microarray gene expression analysis of gastric dysplasia of Tff1 -/- mice was compared to that of normal gastric mucosa of wild-type mice. The genes most overexpressed in Tff1-/- mice included claudin-7 (CLDN7), early growth response-1 (EGR1), and epithelial membrane protein-1 (EMP1). Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that Cldn7 was overexpressed in all 10 Tff1-/- gastric dysplasia samples. Comparison with our serial analysis of gene expression database of human gastric cancer revealed similar deregulation in human gastric cancers. Quantitative real-time reverse transcriptase-polymerase chain reaction of human gastric adenocarcinoma samples indicated that, of these three genes, CLDN7 was the most frequently up-regulated gene. Using immunohistochemistry, both mouse and human gastric glands overexpressed Cldn7 in dysplastic but not surrounding normal glands. Cldn7 expression was observed in 30% of metaplasia, 80% of dysplasia, and 70% of gastric adenocarcinomas. Interestingly, 82% of human intestinal-type gastric adenocarcinomas expressed Cldn7 whereas diffuse-type gastric adenocarcinomas did not (P < 0.001). These results suggest that Cldn7 expression is an early event in gastric tumorigenesis that is maintained throughout tumor progression.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalAmerican Journal of Pathology
Volume167
Issue number2
DOIs
StatePublished - Aug 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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