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 ␣2,3 sialyltransferase studied here is particularly relevant to the study of breast cancer since the activity of the enzyme is elevated in breast cancer cell lines (Brockhausen et al., 1995) . Using in situ hybridization, we have also recently noted elevation of expression of the mRNA coding for the enzyme in some primary breast cancers, with the less differentiated tumors showing a higher expression (Burchell, J., and R. Poulsom, manuscript in preparation) . The data presented here show that increasing the expression of the ␣2,3 sialyltransferase in breast epithelial cell lines results in increased sialylation of the O-glycans added to the MUC1 glycoprotein, manifest as an increase in sialylated core-1 structures. Moreover, the enzyme may compete with the core-2 ␤1,6 GlcNAc transferase (when it is expressed) for the common core-1 substrate with the result that the GlcNAc content of the O-glycans is reduced (Fig. 7) . Although the core-2 ␤1,6 GlcNAc T is absent in some breast cancer cell lines, in others such as MCF-7, mRNA and enzyme activity have been demonstrated (Brockhausen et al., 1995) . Our results indicate that the increase in the ␣2,3 SAT (O) activity seen in the breast cancers could still inhibit chain extension and influence the composition of the O-glycans added to a tumor-associated antigen, even when the core-2 ␤1,6