title: Cyclooxygenase-2 enzyme induces the expression of the α-2,3-sialyltransferase-3 (ST3Gal-I) in breast cancer.
abstract: Aberrant glycosylation is a common feature of malignant change. Changes in mucin-type O-linked glycosylation in breast cancer can result in the expression of truncated core 1-based sialylated glycans rather than the core 2-based glycans observed in normal mammary epithelium cells. This has been shown, in part, to be due to changes in the expression of glycosyltransferases, including the up-regulation of some sialyltransferases. Using the breast cancer cell line T47D, we have shown that PGE2, one of the final products of the cyclooxygenase-2 (COX-2) pathway, can induce the mRNA expression of the sialyltransferase α-2,3-sialyltransferase-3 (ST3Gal-I), resulting in increased sialyltransferase activity, demonstrated by a reduction in PNA lectin staining. Induction of COX-2 in the MDA-MB-231 breast cancer cell line also results in the increased expression of ST3Gal-I, leading to increased sialylation of the substrate of ST3Gal-I, core 1 Galβ1,3GalNAc. This effect on sialylation could be reversed by the selective COX-2 inhibitor celecoxib. The use of siRNA to knock down COX-2 and overexpression of COX-2 in MDA-MD-231 cells confirmed the involvement of COX-2 in the up-regulation of ST3Gal-I. Moreover, analysis of the expression of ST3Gal-I and COX-2 by 74 primary breast cancers showed a significant correlation between the two enzymes. COX-2 expression has been associated with a number of tumors, including breast cancer, where its expression is associated with poor prognoses. Thus, these results suggest the intriguing possibility that some of the malignant characteristics associated with COX-2 expression may be via the influence that COX-2 exerts on the glycosylation of tumor cells.
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Daisy
authors.initials: D
authors.lastname: Sproviero
authors.forename: Sylvain
authors.initials: S
authors.lastname: Julien
authors.forename: Brian
authors.initials: B
authors.lastname: Burford
authors.forename: Joyce
authors.initials: J
authors.lastname: Taylor-Papadimitriou
authors.forename: Joy M
authors.initials: JM
authors.lastname: Burchell
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D051546:Cyclooxygenase 2; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human