Gene cloning of a novel apomucin expressed in human gastric surface epithelia and parietal cells

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Three mouse monoclonal antibodies, i.e. SO-MU1,2, and 3, were established using deglycosylated human gastric mucin as antigen. We used SO-MU1 in the present study.A cDNA fragment, m-8, was cloned by screening of human gastric cDNA expression lambdagt11 library with SO-MU1. It had the size of 1095 bp and contained 24 nucleotide tandem repeats characteristic for MUC5AC.Thus SO-MU1 was the first monoclonal antibody for MUC5AC.MUC5AC detected with SO-MU1 was found in the normal gastric surface epithelial cells, gastric parietal cells, small intestinal epithelial cells, and biliary tract epitheliae, but was not found in the large intestinal epithelial cells, parenchymal liver cells, and pancreatic acinal and ductal epithelial cells. The observed distribution differed partly from that previously reported using the polyclonal antibody raised against the synthetic tandem repeat peptide. We suggested that the reactivity of SO-MU1 was not affected by glycosylation of the tandem repeat domains.Gastric metaplastic epithelial cells and the goblet cells of colon polyp expressed MUC5AC.The MUC5AC expression by gastric cancers was dependent on their histological classification. Colon cancers did not express MUC5AC.Pancreatic cancers, especially the well differentiated cancers, expressed MUC5AC.These results suggested that switching of apomucin subtype expression was one of the molecular mechanism for the carbohydrate antigen phenotype abnormality in the differential disorders.The preliminary study suggested that plasma CA19-9 was carried by MUC5AC in pancreatic cancer patients, but not in gastrointestinal cancer patients. It seemed possible to increase the diagnostic specificity of carbohydrate tumor markers with the use of antibodies against their apoproteins.