title: Polypeptide GalNAc-transferases, ST6GalNAc-transferase I, and ST3Gal-transferase I expression in gastric carcinoma cell lines.
abstract: Mucin O-glycosylation in cancer is characterized by aberrant expression of immature carbohydrate structures leading to exposure of simple mucin-type carbohydrate antigens and peptide epitopes. Glycosyltransferases controlling the initial steps of mucin O-glycosylation are responsible for the altered glycosylation observed in cancer. We studied the expression in gastric cell lines of six UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-T1, T2, T3, T4, T6, T11) that catalyze the initial key step in the regulation of mucin O-glycosylation, the transfer of GalNAc from UDP-GalNAc to serine and threonine residues. We also studied the expression of ST6GalNAc-I, the enzyme responsible for the synthesis of Sialyl-Tn antigen (NeuAcalpha2,6GalNAc) and the ST3Gal-I, the enzyme responsible for the synthesis of Sialyl-T antigen (NeuAcalpha2,3Galbeta1,3GalNAc). This study was done using specific monoclonal antibodies, enzymatic assays, and RT-PCR. Our results showed that GalNAc-T1, -T2, and -T3 have an ubiquitous expression in all gastric cell lines, whereas GalNAc-T4, -T6, and -T11 show a restricted expression pattern. The immunoreactivity with MAb VU-2-G7 suggests that, apart from GalNAc-T4, another GalNAc transferase is involved in the glycosylation of the Thr in the PDTR region of the MUC1 tandem repeat. The expression of ST3Gal-I correlates with the expression of the Sialyl-T antigen in gastric cell lines and in the control cell lines studied. The expression of ST6GalNAc-I is low in gastric cell lines, in accordance with the low/absent expression of the Sialyl-Tn antigen.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors.forename: Nuno T
authors.initials: NT
authors.lastname: Marcos
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruz
authors.forename: Filipe
authors.initials: F
authors.lastname: Silva
authors.forename: Raquel
authors.initials: R
authors.lastname: Almeida
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.forename: Silvia
authors.initials: S
authors.lastname: Von Mensdorff-Pouilly
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
mesh_terms: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012799:Sialyltransferases / Q000276:immunology / Q000378:metabolism*; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D018396:Mucin-1; D017350:N-Acetylgalactosaminyltransferases; D012799:Sialyltransferases; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human