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Gene alterations of glycosyltransferase during the course of malignant tranformation in uterine endometrium

子宫内膜恶变过程中糖基转移酶基因的改变

基本信息

批准号：
06671685
负责人：
AOKI Daisuke
金额：
$ 1.41万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

Monoclonal antibody MSN-1 was established against an endometrial cancer cell line and proven to recognize at least Lewis b carbohydrate antigen. Immunohistochemical staining with this antibody resulted in a positive reaction in more than 85% of the endometrial adenocarcinoma cases examined but in few cases with normal endometria, indicating that MSN-1-reactive antigen is able to be a good histochemical marker for endometrial cancers. Expression of the Lewis histo-blood group antigen is determined by the Lewis type alpha (1,3/1,4) fucosyltransferase enconded by the FucT-III gene (Le gene). Since Lewis-negative individuals are known to be homozygous for an allele with missense mutations of this gene (le/le) which cause inactivation of the enzyme activity, we investigated whether or not phenotypic expression of the MSN-1-reactive antigen in endometrial adenocarcinoma specimens was affected by the genotypes of the FucT-III gene in patients with adenocarcinoma. To determine the genotypesof the FucT-III gene, i.e., to detect the mutations, we employed the polymerase chain reaction (PCR) -restriction fragment length polymorphism method by using genomic DNAs extracted from the patients'peripheral blood leucocytes as PCR templates. Out of 59 cases of endometrial adenocarcinoma, four cases with the Lewis-negative genotype (le/le) were identified and examined by the ABC immunohistochemical technique for the presence of the MSN-1-reactive antigen on their cancer cells. The conventional hemagglutination reaction also revealed all four of these cases to have the Lewis-negative blood type. However, their cancer tissues reacted positively with MSN-1. These results suggest that MSN-1 recognizes a fucosylated carbohydrate that is constructed by fucosyltransferases other than FucT-III.

针对子宫内膜癌细胞系建立了单克隆抗体MSN-1，并证明其至少识别刘易斯B糖抗原。免疫组化染色与此抗体导致阳性反应，在85%以上的子宫内膜腺癌的情况下检查，但在少数情况下，正常子宫内膜，表明MSN-1反应性抗原是一个很好的组织化学标记子宫内膜癌。刘易斯组织血型抗原的表达由FucT-III基因（Le基因）编码的刘易斯型α（1，3/1，4）岩藻糖基转移酶决定。由于路易斯阴性个体是纯合子的等位基因与错义突变的这个基因（le/le），导致失活的酶活性，我们调查是否表型表达的MSN-1反应性抗原在子宫内膜腺癌标本是受影响的基因型的FucT-III基因在腺癌患者。为了确定FucT-III基因的基因型，即，为了检测突变，我们采用聚合酶链反应（PCR）-限制性片段长度多态性方法，以从患者外周血白细胞中提取的基因组DNA作为PCR模板。在59例子宫内膜腺癌中，4例Lewis阴性基因型（le/le）被确定，并通过ABC免疫组化技术检查其癌细胞上MSN-1反应抗原的存在。常规的血凝反应也显示所有这四个病例都有路易斯阴性血型。然而，他们的癌组织与MSN-1呈阳性反应。这些结果表明，MSN-1识别由岩藻糖基转移酶而不是FucT-III构建的岩藻糖基化碳水化合物。