Canonical Wnt Signaling Pathway Plays an Essential Role in N-Methyl-N-Nitrosurea Induced Gastric Tumorigenesis of Mice

Abstract

Deregulated Wnt signaling pathway is implicated in many hereditary diseases and tumorigenesis including colorectal cancer, hepatocellular carcinoma and gastric cancer. In this study, to assess the relationship between chemically induced gastric tumor and canonical Wnt signaling pathway in genetically intact mice, histopathological and quantitative mRNA analyses were performed in C57BL/6J mice given drinking water containing N-methyl- N-nitrosurea (MNU). 60.5% of gastric adenoma and 27.9% of adenocarcinoma were observed 48 weeks after first administration. Also, in immunohistochemical analysis, aberrant expressions of phospho-GSK-3β, β-catenin, cyclin D1, c-Myc, osteopontin and COX-2 were found. In double immunofluorescent-antibody stains, β-catenin accumulation was colocalized with other proteins. mRNA levels of cyclin D1, c-myc and COX-2 were relatively higher in adenocarcinoma. Altogether, canonical Wnt pathway was highly involved in MNU induced gastric neoplasia of C57BL/6J mice, and it could be a considerably suitable system for the study to examine the linkage between gastric tumorigenesis and the canonical Wnt pathway.