Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism

Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism
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DOI：
10.1093/glycob/cwi027
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发表时间：
2005-05-01
期刊：
GLYCOBIOLOGY
影响因子：
4.3
通讯作者：
Hollingsworth, MA
Hollingsworth, MA
中科院分区：
生物学3区
文献类型：
--
作者：
Santos-Silva, F;Fonseca, A;Hollingsworth, MA

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粘蛋白的异常糖基化是与致癌转化相关的常见现象。我们研究了一系列胃癌中肿瘤相关抗原T、Tn和唾液酸-Tn的表达与MUC 1粘蛋白串联重复序列长度多态性之间的关系。我们进一步评估了MUC 1串联重复序列长度对这些肿瘤相关碳水化合物抗原（TACAs）表达的相关性，使用表达携带0、3、9和42个重复序列的重组MUC 1构建体的胃癌细胞系模型。胃癌显示出高患病率的Tn和唾液酸-Tn抗原，而T抗原表达频率较低。MUC 1大串联重复等位基因纯合子胃癌患者T抗原表达显著增高。未发现Tn和唾液酸-Tn抗原的显著相关性。胃癌细胞系模型实验加强了这种新的关联，其中在用更大的VNTR区域转染的克隆中检测到T抗原的从头表达。我们的研究结果表明，MUC 1串联重复序列的多态性影响TACA在胃癌细胞中的表达，因此可能允许识别出表达T抗原的更具侵袭性肿瘤的患者亚组。
Aberrant glycosylation of mucins is a common phenomenon associated with oncogenic transformation. We investigated the association between expression of the tumor-associated antigens T, Tn, and sialyl-Tn and polymorphism in the length of the MUC1 mucin tandem repeat in a series of gastric carcinomas. We further evaluated the relevance of MUC1 tandem repeat length on the expression of these tumor-associated carbohydrate antigens (TACAs) using a gastric carcinoma cell line model expressing recombinant MUC1 constructs carrying 0, 3, 9, and 42 repeats. Gastric carcinomas showed a high prevalence of Tn and sialyl-Tn antigens, whereas T antigen was less frequently expressed. The expression of T antigen was significantly higher in gastric carcinomas from patients homozygous for MUC1 large tandem repeat alleles. No significant associations were found for Tn and sialyl-Tn antigens. This novel association was reinforced by the gastric carcinoma cell line model experiments, where de novo expression of T antigen was detected in clones transfected with larger VNTR regions. Our results indicate that polymorphism in the MUC1 tandem repeat influences the expression of TACAs in gastric cancer cells and may therefore allow the identification of subgroups of patients that develop more aggressive tumors expressing T antigen.