Expression of Tight-Junction Protein Claudin-7 Is an Early Event in Gastric Tumorigenesis
| Autor: | James K. Roche, Adam H. Johnson, Henry F. Frierson, Steven M. Powell, Wael El-Rifai, Sheila E. Crowe, Alexander Zaika, Christopher A. Moskaluk |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Pathology medicine.medical_specialty Receptors Cell Surface Adenocarcinoma Biology Immediate early protein Immediate-Early Proteins Tight Junctions Pathology and Forensic Medicine Mice Stomach Neoplasms Metaplasia Gastric glands medicine Gastric mucosa Animals Humans Aged Early Growth Response Protein 1 Oligonucleotide Array Sequence Analysis Aged 80 and over Mice Knockout Gene Expression Profiling Tumor Suppressor Proteins Stomach digestive oral and skin physiology Membrane Proteins Estrogens Middle Aged medicine.disease Growth Inhibitors digestive system diseases Neoplasm Proteins DNA-Binding Proteins Original Research Paper Gastric Dysplasia medicine.anatomical_structure Gastric Mucosa Dysplasia Claudins Cancer research Female Trefoil Factor-1 medicine.symptom Transcription Factors |
| Zdroj: | The American Journal of Pathology. 167:577-584 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)62999-9 |
| Popis: | Trefoil factor-1 (Tff1) expression is remarkably down-regulated 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. |
| Databáze: | OpenAIRE |
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