Identification and Functional Characterization of a Human GalNAc α2,6-Sialyltransferase with Altered Expression in Breast Cancer

Abstract

Background: We sought to identify genes with altered expression during human breast cancer progression by applying mRNA comparisons of normal and tumor mammary cell lines with increasingly malignant phenotypes. The gene encoding a new sialyltransferase (STM) was found to be down-regulated in tumor cells. Abnormal expression and enzymatic activities of sialyltransferases in tumor cells result in the formation of tumor-associated carbohydrate antigens that can be used for the better understanding of the disease process and are applied for tumor diagnosis and immunotherapy. Altered glycosylation patterns of the MUC1 mucin, in particular, is a target antigen for immunotherapy of breast and other cancers. Materials and Methods: Total RNAs from multiple normal mammary epithelial cell strains and tumor cell lines were compared by differential display and the differential expression of selected cDNAs was confirmed by Northern analyses. Recombinant STM was expressed in COS-7 cells. The substrate and linkage specificity of STM was examined using various oligosaccharides and O-glycosylated proteins as acceptor substrates. The chromosomal localization of the SIATL1 gene was assigned by somatic cell hybrid analysis. Results: A human sialyltransferase gene was identified by differential display as being down-regulated in breast tumor cell lines as compared to normal mammary epithelial

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

“…In breast cancer, the sialyltransferase (α2,3-st), is mainly responsible for catalyzing sialic acid to form α2,3-sialic acid residues (26). In this study, we analyzed the mrnA level of α2,3-st gene in breast cancer cell lines.…”

Human M-Ficolin Is a Secretory Protein That Activates the Lectin Complement Pathway

“…In addition, M-ficolin bound to N-acetylgalactosamine and sialic acid. Sialic acid plays important roles as a receptor for molecules that regulate cellular growth, differentiation, cell-cell communication, and adhesion (32). The biological meaning of this carbohydrate recognition of M-ficolin is unknown; however, this finding, in conjuction with the observation that M-ficolin was expressed in pulmonary alveolar epithelial cells, suggests that M-ficolin might have broad functions in local immunity.…”

Functional Diversity of Mammalian Sialyltransferases

“…ST6GalNAc-I and -II constitute the 2 members of the first subfamily. They exhibit similar substrate specificity, utilizing mainly GalNAc, Galβ1,3GalNAc, and Siaα2,3Galβ1,3GalNAc structures on the O-glycans of glycoproteins as acceptor substrates (86)(87)(88)(89)(90)(91)(92). ST6GalNAc-I is thought to be responsible for the synthesis of the tumor-associated sialyl-Tn antigen (Siaα2,6GalNAc-O-Ser/Thr) (87,(93)(94)(95), whereas ST6GalNAc-II mediates the synthesis of the sialyl-Tn antigen on IgA1 in IgA nephropathy (91).…”