α１，４‐Ｎ‐アセチルグルコサミン転移酵素と消化器病学

Abstract

Mucous glycoproteins secreted from the gastroduodenal mucosa and pancreatic duct showing gastric metaplasia characteristically contain GlcNAcα1→4Galβ→R structures in terminal ends of O-glycans, and this unique carbohydrate is frequently expressed in gastric cancer cells. We have isolated a cDNA encoding human α1, 4-N-acetylglucosaminyltransferase (α4GnT) responsible for the biosynthesis of GlcNAcα1 →4Galβ→R by expression cloning and characterized the substrate specificity and tissue localization of this enzyme. Using an antibody specific for α4GnT, we then demonstrated that this enzyme is frequently expressed in gastric cancer cells but not in peripheral blood cells. Thus, the expression level of α4GnT mRNA in the mononuclear cell fraction of peripheral blood was quantitatively measured using real-time RT-PCR to detect the circulating tumor cells. The transcripts of α4GnT were detected in 26 patients (63.4%) of gastric cancer patients but not in any of 23 healthy volunteers examined. In chronic active gastritis, 3 patients (33.3%) were positive for this assay, but the relative amounts of α4GnT mRNA to GAPDH mRNA in the chronic gastritis patients were 30-fold lower than those of the gastric cancer patients. Surprisingly, the transcripts of α4GnT were detectable even in early gastric cancer patients, when the cancer cells were limited to the submucosal layer. In addition, the expression level of the α4GnT was increased in association with the tumor progression. These combined results indicate that the quantitative analysis of α4GnT mRNA in the peripheral blood based on the real-time RT-PCR is useful for the detection of gastric cancer.