Polypeptide GalNAc-transferases, ST6GalNAc-transferase I, and ST3Gal-transferase I expression in gastric carcinoma cell lines

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-GaINAc:polypeptide N-acetylgalactosaminyl-transferases (GaINAc-T1, T2, T3, T4, T6, T11) that catalyze the initial key step in the regulation of mucin O-glycosylation, the transfer of GaINAc from UDP-GaINAc to serine and threonine residues. We also studied the expression of ST6GaINAc-I, the enzyme responsible for the synthesis of Sialyl-Tn antigen (NeuAcalpha2,6GaINAc) and the ST3GaI-I, the enzyme responsible for the synthesis of Sialyl-T antigen (NeuAcalpha2,3GaIbeta1,3GaINAc). This study was done using specific monoclonal antibodies, enzymatic assays, and RT-PCR. Our results showed that GaINAc-T1, -T2, and -T3 have an ubiquitous expression in all gastric cell lines, whereas GaINAc-T4, -T6, and -T11 show a restricted expression pattern. The immunoreactivity with MAb VU-2-G7 suggests that, apart from GaINAc-T4, another GaINAc transferase is involved in the glycosylation of the Thr in the PDTR region of the MUC1 tandem repeat. The expression of ST3GaI-I correlates with the expression of the Sialyl-T antigen in gastric cell lines and in the control cell lines studied. The expression of ST6GaINAc-I is low in gastric cell lines, in accordance with the low/absent expression of the Sialyl-Tn antigen.