A Transfected Sialyltransferase That Is Elevated in Breast Cancer and Localizes to the medial/trans-Golgi Apparatus Inhibits the Development of core-2–based O-Glycans

Whitehouse, Caroline; Burchell, Joy; Gschmeissner, Stephen; Brockhausen, Inka; Lloyd, Kenneth O.; Taylor-Papadimitriou, Joyce

The key glycosyltransferases involved in the changes seen in breast malignancies are the ␣ 2,3 sialyltransferase (EC 2.4.99.4) , which adds sialic acid to Gal ␤ 1,3 GalNAc (core-1), and the ␤ 1,6 N -acetyld -glucosamine (GlcNAc) transferase (EC 2.4.1.102), which forms core-2 from core-1 and is crucial for chain branching ( Fig. 1 ) (Kuhns et al., 1993) . These enzymes use the same substrate, and their effect is to terminate or initiate chain branching leading to extension, respectively. We have recently observed that the activity of the chain terminating enzyme, ␣ 2,3 sialyltransferase, is increased 8-10-fold in some breast cancer cell lines, while core-2 ␤ 1,6 GlcNAc T activity is either lost or reduced (Brockhausen et al., 1995) . The expression of the MUC1 mucin is upregulated in breast cancers and the difference in glycosylation pattern causes the cancer-associated mucin to be antigenically distinct from the normal mucin. MUC1-based immunogens are therefore prime candidates for cancer vaccines and several formulations are being tested in the clinic.