Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family

被引:100
作者
Mandel, U
Hassan, H
Therkildsen, MH
Rygaard, J
Jakobsen, MH
Juhl, BR
Dabelsteen, E
Clausen, H
机构
[1] Univ Copenhagen, Sch Dent, Fac Hlth Sci, Dept Oral Diagnost, DK-2200 Copenhagen N, Denmark
[2] Roskilde Cty Hosp, Dept Pathol, Roskilde, Denmark
[3] Rigshosp, Bartholin Inst, Copenhagen, Denmark
[4] Rigshosp, Dept Otolaryngol Head & Neck Surg, Copenhagen, Denmark
[5] Rigshosp, Dept Pathol, Copenhagen, Denmark
关键词
polypeptide GalNAc-transferases; O-glycosylation; monoclonal antibodies; squamous cell carcinomas; epithelial differentiation;
D O I
10.1093/glycob/9.1.43
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc: polypeptide N-acetyl-galactosaminyltransferases (GalNAc-transferases). Individual GalNAc-transferases appear to have different functions and Northern analysis indicates that they are differently expressed in different organs. This suggests that O-glycosylation may vary with the repertoire of GalNAc-transferases expressed in a given cell. In order to study the repertoire of GalNAc-transferases in situ in tissues and changes in tumors, we have generated a panel of monoclonal antibodies (MAbs) with well defined specificity for human GalNAc-T1, -T2, and -T3. Application of this panel of novel antibodies revealed that GalNAc-transferases are differentially expressed in different cell lines, in spermatozoa, and in oral mucosa and carcinomas. For example, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, and GalNAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa, The expression patterns in normal oral mucosa were found to vary with cell differentiation, and for GalNAc-T2 and -T3 this was reflected in oral squamous cell carcinomas. The expression pattern of GalNAc-T1 was on the other hand changed in tumors to either total loss or expression in cytological poorly differentiated tumor cells, where the normal undifferentiated cells lacked expression. These results demonstrate that the repertoire of GalNAc-transferases is different in different cell types and vary with cellular differentiation, and malignant transformation. The implication of this is not yet fully understood, but it suggests that specific changes in sites of O-glycosylation of proteins may occur as a result of changes in the repertoire of GalNAc-transferases.
引用
收藏
页码:43 / 52
页数:10
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