TY  - JOUR
AU  - Sewell, R.
AU  - Bäckstrom, M.
AU  - Dalziel, M.
AU  - Gschmeissner, S.
AU  - Karlsson, H.
AU  - Noll, T.
AU  - Gätgens, J.
AU  - Clausen, H.
AU  - Hansson, G.
AU  - Burchell, J.
AU  - Taylor-Papadimitriou, J.
TI  - The ST6GalNAc-l sialyltransferase localises throughout the Golgi and is responsible for the synthesis of the tumour associated sialyl Tn O-glycan in human breast cancer
JO  - The journal of biological chemistry
VL  - 281
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - PreJuSER-49189
SP  - 3586 - 3594
PY  - 2006
N1  - Record converted from VDB: 12.11.2012
AB  - The functional properties of glycoproteins are strongly influenced by their profile of glycosylation, and changes in this profile are seen in malignancy. In mucin-type O-linked glycosylation these changes can result in the production of mucins such as MUC1, carrying shorter sialylated O-glycans, and with different site occupancy. Of the tumor-associated sialylated O-glycans, the disaccharide, sialyl-Tn (sialic acid alpha2,6GalNAc), is expressed by 30% of breast carcinomas and is the most tumor-specific. The ST6GalNAc-I glycosyltransferase, which can catalyze the transfer of sialic acid to GalNAc, shows a highly restricted pattern of expression in normal adult tissues, being largely limited to the gastrointestinal tract and absent in mammary gland. In breast carcinomas, however, a complete correlation between the expression of RNA-encoding ST6GalNAc-I and the expression of sialyl-Tn is evident, demonstrating that the expression of sialyl-Tn results from switching on expression of hST6GalNAc-I. Endogenous or exogenous expression of hST6GalNAc-I (but not ST6GalNAc-II) always results in the expression of sialyl-Tn. This ability to override core 1/core 2 pathways of O- linked glycosylation is explained by the localization of ST6GalNAc-I, which is found throughout the Golgi stacks. The development of a Chinese hamster ovary (CHO) cell line expressing MUC1 and ST6GalNAc-I allowed the large scale production of MUC1 carrying 83% sialyl-Tn O-glycans. The presence of ST6GalNAc-I in the CHO cells reduced the number of O-glycosylation sites occupied in MUC1, from an average of 4.3 to 3.8 per tandem repeat. The availability of large quantities of this MUC1 glycoform will allow the evaluation of its efficacy as an immunogen for immunotherapy of MUC1/STn-expressing tumors.
KW  - Animals
KW  - Antigens, Neoplasm: chemistry
KW  - Antigens, Tumor-Associated, Carbohydrate: chemistry
KW  - Blotting, Northern
KW  - Blotting, Western
KW  - Breast Neoplasms: enzymology
KW  - Breast Neoplasms: pathology
KW  - CHO Cells
KW  - Cell Line, Tumor
KW  - Chromatography, Liquid
KW  - Cloning, Molecular
KW  - Cricetinae
KW  - Female
KW  - Flow Cytometry
KW  - Glycosylation
KW  - Golgi Apparatus: enzymology
KW  - Golgi Apparatus: metabolism
KW  - Humans
KW  - Immunotherapy: methods
KW  - K562 Cells
KW  - Mammary Glands, Human: metabolism
KW  - Microscopy, Fluorescence
KW  - Microscopy, Immunoelectron
KW  - Models, Chemical
KW  - Polysaccharides: chemistry
KW  - Polysaccharides: metabolism
KW  - Recombinant Fusion Proteins: chemistry
KW  - Reverse Transcriptase Polymerase Chain Reaction
KW  - Sialyltransferases: chemistry
KW  - Sialyltransferases: metabolism
KW  - Spectrometry, Mass, Electrospray Ionization
KW  - Transfection
KW  - Antigens, Neoplasm (NLM Chemicals)
KW  - Antigens, Tumor-Associated, Carbohydrate (NLM Chemicals)
KW  - Polysaccharides (NLM Chemicals)
KW  - Recombinant Fusion Proteins (NLM Chemicals)
KW  - sialosyl-Tn antigen (NLM Chemicals)
KW  - Sialyltransferases (NLM Chemicals)
KW  - CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:16319059
UR  - <Go to ISI:>//WOS:000235128200070
DO  - DOI:10.1074/jbc.M511826200
UR  - https://juser.fz-juelich.de/record/49189
ER  -