UDP-GalNAc:Fuc{alpha}1-2Gal{alpha}1-3GalNAc transferase activity in hamster pancreatic cancers and in normal hamster alimentary tissues |
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Authors: | Hirota, Masahiko Pour, Parviz M. Chaney, William G. |
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Affiliation: | 1The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center Omaha, NE 681984525, USA 2Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center Omaha, NE 681984525, USA |
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Abstract: | Ductal adenocarcinomas induced by N-nitrosobis(2-oxopropyl)aminetreatment in Syrian hamsters produce blood group-A antigen,which is not present in normal hamster pancreas. To understandthe underlying mechanism of A antigen neoexpression in pancreaticcancer cells, we examined the activity of UDP-GalNAc: Fuc12Gal13GalNActransferase (A-transferase), the enzyme responsible for bloodgroup-A antigen production. The specific activity of A-transferasein the pancreatic cancers was 8 nmol/mg protein/h in membranepreparations, 0.3 nmol/mg protein/h in whole cell extracts,and undetectable in normal hamster pancreas. Significant A-transferaseactivity was found in normal tissues expressing blood group-Aantigen. Although both normal (gastric antrum, colon) and pancreaticcancer cells showed similar enzymatic characteristics (optimalpH, substrate affinity, optimal [Mn2+]), there was a differencein the requirement for divalent cations. The A-transferase incancer cells showed a more stringent requirement for Mn2+. Theseresults suggest that A-transferase is activated during nitrosamine-inducedpancreatic carcinogenesis, which results in the neoexpressionof blood group-A antigen. The difference in divalent cationrequirements between A-transferase activities of cancer andnormal cells may indicate that there are multiple A-transferasespresent in hamster tissues. |
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