Journal
ACTA HISTOCHEMICA
Volume 109, Issue 4, Pages 273-284Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.acthis.2007.02.009
Keywords
glycosylation; breast cancer; polypeptide; N-acetylgalactosaminyltransferases; ppGalNAc-T; immunocytochemistry; Helix pomatia agglutinin; HPA
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An extensive family of UDP-N-alpha-D-gatactosamine: potypepticle N-acetylgatactosaminyltransferases (potypeptide N-acetylgatactosaminyltransferases, ppGalNAc-T's) catalyse the attachment of the first N-acetylgalactosamine (GalNAc) monosaccharide to the potypepticle at the initiation of O-tinked glycosylation of proteins. Some members of the famity are broadly expressed while others are more restricted in their distribution, their expression and activity being confined to certain cells or tissues, being associated with physiological states or differentiation. Their careful regutation, which is not welt understood, may mediate the synthesis of varied glycoforms of cellular proteins with different biological. activities. Disruptions in glycosylation are a common feature of cancer and may have functional significance. Immunocytochemistry with confocal scanning laser microscopy was employed to detect members of the ppGalNAc-T famity, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell tines. The cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT 3522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic breast cancer (ZR75-1, T47D, MCF-7, DU 4475). They stably synthesise varying levels, consistent with origin and phenotype, of aberrantly glycosytated glycoproteins featuring exposed, terminal GalNAc residues, including the cancer-associated Tn antigen, which, in numerous studies, have been associated with metastatic competence and poor cancer prognosis. GalNAc-T1 and -T2 were detectable at low levels in all cell lines studied. ppGalNAc-T4, which has never been described in breast, was very weakly detectable in BT 474, MCF7 and T47D. ppGalNAc-T3 and -T6 were weakly detectable or undetectable, respectively, in the cell line HMT 3522 derived from 'normal'/benign breast epithelium, but were readily detectable in at[ malignant cell lines. Thus, a broader range of ppGalNAc-T's were detectable in the malignant cell lines in comparison to the 'normal'/benign cells, where only the 'housekeeping' ppGalNAc-T1 and -T2 were present. Expression of normally tightly restricted ppGalNAc-T's may result in initiation of O-tinked glycosylation at normally unoccupied potential glycosylation sites leading to altered glycoforms of proteins with changed biological activity which may contribute to the pathogenesis of cancer. (c) 2007 Elsevier GmbH. All rights reserved.
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