UDP-GalNAc:Fuc alpha 1-2Gal alpha 1-3GalNAc transferase activity in hamster pancreatic cancers and in normal hamster alimentary tissues.
Ductal adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine treatment in Syrian hamsters produce blood group-A antigen, which is not present in normal hamster pancreas. To understand the underlying mechanism of A antigen neoexpression in pancreatic cancer cells, we examined the activity of UDP-GalNAc:Fuc alpha 1-2Gal alpha 1-3GalNAc transferase (A-transferase), the enzyme responsible for blood group-A antigen production. The specific activity of A-transferase in the pancreatic cancers was approximately 8 nmol/mg protein/h in membrane preparations, 0.3 nmol/mg protein/h in whole cell extracts, and undetectable in normal hamster pancreas. Significant A-transferase activity was found in normal tissues expressing blood group-A antigen. Although both normal (gastric antrum, colon) and pancreatic cancer cells showed similar enzymatic characteristics (optimal pH, substrate affinity, optimal [Mn2+]), there was a difference in the requirement for divalent cations. The A-transferase in cancer cells showed a more stringent requirement for Mn2+. These results suggest that A-transferase is activated during nitrosamine-induced pancreatic carcinogenesis, which results in the neoexpression of blood group-A antigen. The difference in divalent cation requirements between A-transferase activities of cancer and normal cells may indicate that there are multiple A-transferases present in hamster tissues.
Hirota
M
M
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-4525.
Pour
P M
PM
Chaney
W G
WG
D000818:Animals; D002240:Carbohydrate Sequence; D002413:Cations, Divalent; D002478:Cells, Cultured; D006224:Cricetinae; D004064:Digestive System / Q000201:enzymology*; D005646:Fucosyl Galactose alpha-N-Acetylgalactosaminyltransferase / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D002413:Cations, Divalent; D005646:Fucosyl Galactose alpha-N-Acetylgalactosaminyltransferase