Expression of Core 2 β-1,6-N-Acetylglucosaminyltransferase in a Human Pancreatic Cancer Cell Line Results in Altered Expression of MUC1 Tumor-associated Epitopes

作者: Paul V. Beum , Jaswant Singh , Michael Burdick , Michael A. Hollingsworth , Pi-Wan Cheng

DOI: 10.1074/JBC.274.35.24641

关键词:

摘要: Many tumor-associated epitopes possess carbohydrate as a key component, and thus changes in the activity of glycosyltransferases could play role generating these epitopes. In this report we describe stable transfection human pancreatic adenocarcinoma cell line, Panc1-MUC1, with cDNA for mucin core 2 GlcNAc-transferase (C2GnT), which creates β-1,6 branch mucin-type glycans. These cells lack endogenous C2GnT but express recombinant MUC1 cDNA. C2GnT-transfected clones expressing different levels were characterized using monoclonal antibodies CC49, CSLEX-1, SM-3, recognize Increased expression led to greatly diminished CC49 epitope, identified NeuAcα2,6(Galβ1,3)GalNAcα-Ser/Thr Panc1-MUC1 cells. This was accompanied by emergence CSLEX-1 sialyl Lewis x (NeuAcα2,3Galβ1,4(Fucα1,3)GlcNAc-R), an important selectin ligand. Despite this, however, transfectants not bind selectins. also masking SM-3 peptide persisted after removal sialic acid, further suggesting greater complexity 2-associated O- glycans on MUC1. The results study suggest that regulatory certain

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