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The analysis on functions of aberrant carbohydrates in endometrial cancer cells and the mechanism of their expression

子宫内膜癌细胞中异常碳水化合物的功能及其表达机制分析

基本信息

批准号：
10671570
负责人：
AOKI Daisuke
金额：
$ 2.11万
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：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Monoclonal antibody MSN-1 was established against an endometrial cancer cell line. Immunohistochemical staining with this antibody resulted in a positive reaction in more than 90% of the cases of endometrial adenocarcinoma examined : but few cases with normal endometria. Base on these histochemical data, all cancer tissues expressing either Lewis b or Lewis y carbohydrate antigen were MSN-1-positive, indicating that the antigen detected by it is significantly increased in the cancer and that its epitope may be a terminal α-1,2 fucosylated carbohydrate residue, which is common between Lewis b and Lewis y. In this study, we investigated whether or not the phenotypic expression of the MSN-1-reactive antigen in endometrial adenocarcinoma specimens was affected by the expression of α-1,2 fucosyltransferases encoded by the Se or H gene.Firstly, we immunohistochemically examined phenotypic expressions of Le antigens in endometrial adenocarcinoma. Secondly, we relatively compared the expression of Se or H gene between cancer tissues and normal endometria by the method of RT-PCR.In addition, we checked missense mutations of the Se gene, whose homozygote (se/se) causes inactivation of the enzymatic activity.Cancer cells obtained from patients with a missense mutation of the Se gene (se/se). were positively stained by MSN-1. On the other hands, mRNA derived from the H gene, as well as that from the Se gene. was not always expressed more in the endometrial adenocarcinoma than in normal endometria. In addition, the MSN-1 reactive antigen on cancer cells did not link to expression of mRNA of Se or Lewis enzyme.These results imply two possibilities that endometrial cancer-specific fucose might be produced by collaboration of several α-1,2 fucosyltransferases or by a novel one.

针对子宫内膜癌细胞系建立了单克隆抗体 MSN-1。使用该抗体进行的免疫组织化学染色在超过 90% 的子宫内膜腺癌病例中产生阳性反应，但对于正常子宫内膜的病例很少。基于这些组织化学数据，所有表达Lewis b或Lewis y碳水化合物抗原的癌症组织均为MSN-1阳性，表明其检测到的抗原在癌症中显着增加，并且其表位可能是末端α-1,2岩藻糖基化碳水化合物残基，这在Lewis b和Lewis y之间是常见的。在本研究中，我们研究了子宫内膜腺癌标本中MSN-1反应性抗原的表型表达是否受到Se或H基因编码的α-1,2岩藻糖基转移酶表达的影响。首先，我们采用免疫组织化学方法检测了子宫内膜腺癌中Le抗原的表型表达。其次，我们通过RT-PCR的方法比较了癌组织和正常子宫内膜之间Se或H基因的表达。此外，我们检查了Se基因的错义突变，其纯合子（se/se）导致酶活性失活。从Se基因（se/se）错义突变的患者中获得癌细胞。 MSN-1染色呈阳性。另一方面，mRNA源自H基因，也源自Se基因。在子宫内膜腺癌中并不总是比在正常子宫内膜中表达更多。此外，癌细胞上的MSN-1反应性抗原与Se或Lewis酶的mRNA表达无关。这些结果暗示了两种可能性：子宫内膜癌特异性岩藻糖可能是由几种α-1,2岩藻糖基转移酶协作产生的，或者是由一种新型岩藻糖基转移酶产生的。