LAUSR

Highly glycosylated mucins protect epithelial surfaces from external insults and are related to malignant behaviors of carcinoma cells. However, the importance of carbohydrate chains on mucins in the process of cellular protection is not fully understood. Here, we investigated the effect of human mucin-21 (MUC21) expression on the susceptibility to apoptosis. MUC21 transfection into HEK293 cells decreased the number of apoptotic cells in culture media containing etoposide or after ultraviolet light irradiation. We used Chinese hamster ovary (CHO) cell variants to investigate the importance of MUC21 glycosylation in the resistance to apoptosis. When MUC21 was expressed in CHO-K1 cells, it was glycosylated with sialyl T-antigen and the cells showed resistance to etoposide-induced apoptosis. MUC21 transfection into Lec2 cells, a variant of CHO cells lacking sialylation of glycans, revealed that the presence of nonsialylated T-antigen also renders cells resistant to etoposide-induced apoptosis. MUC21 was transfected into ldlD cells and the glycosylation was manipulated by supplementation to the medium. Nonsupplemented cells and cells supplemented with N -acetylgalactosamine showed no resistance to etoposide-induced apoptosis. In contrast, these cells supplemented with N -acetylgalactosamine plus galactose expressed sialyl T-antigen and exhibited resistance to etoposide-induced apoptosis. Finally, galectin-3 knockdown in MUC21 transfectants of HEK293 cells did not significantly affect MUC21-dependent induction of apoptosis resistance. The results suggest that T-antigen with or without sialic acid is essential to the antiapoptotic effect of MUC21. Mucin 21 (MUC21) is a large glycoprotein that protects squamous epithelia. Glycan changes in mucins occur in cancer cells and are thought to contribute to malignant progression. We report glycoform-dependent antiapoptotic effects of MUC21. Various MUC21 glycoforms were expressed in HEK293 and CHO cells. Apoptosis was induced using etoposide or UV exposure. MUC21 with glycans terminated with galactose/sialic acid inhibited apoptosis; MUC21 with no glycans or N -acetylgalactoseamine did not.