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
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
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DOI：
10.1093/glycob/9.1.43
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发表时间：
1999-01-01
期刊：
影响因子：
4.3
通讯作者：
Clausen, H
中科院分区：
文献类型：
--
作者：
Mandel, U;Hassan, H;Clausen, H
粘蛋白O-糖基化是由一大家族的UDP-GalNAc：多肽N-乙酰半乳糖胺转移酶(GalNAc-Transferase)启动的。不同的GalNAc转移酶似乎具有不同的功能，Northern分析表明它们在不同的器官中表达不同。这表明O-糖基化可能随着在特定细胞中表达的GalNAc-转移酶的不同而不同。为了研究GalNAc-转移酶在组织中的原位表达及其在肿瘤中的变化，我们制备了一组针对人GalNAc-T1、-T2和-T3的具有明确特异性的单抗。应用这组新的抗体发现，GalNAc转移酶在不同的细胞系、精子、口腔粘膜和癌症中有不同的表达。例如，GalNAc-T1和-T2在WI38细胞中高表达，而GalNAc-T3在精子中表达，而GalNAc-T1或-T2不表达，在正常口腔粘膜中的表达模式随细胞分化而变化，而GalNAc-T2和-T3的表达模式在口腔鳞癌中有所反映。另一方面，GalNAc-T1在肿瘤中的表达模式改变为完全缺失或在细胞学低分化的肿瘤细胞中表达，而正常未分化的肿瘤细胞缺乏表达。这些结果表明，GalNAc-转移酶在不同的细胞类型中是不同的，并且随着细胞的分化和恶性转化而变化。这一结果的含义尚不完全清楚，但它表明蛋白质O-糖基化位点的特定变化可能是由于GalNAc-转移酶谱系的变化所致。
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.