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

建立了抗子宫内膜癌细胞系的单克隆抗体MSN-1。用该抗体进行免疫组化染色，结果在90%以上的子宫内膜腺癌病例中呈阳性反应，但在正常子宫内膜中则很少。基于这些组织化学数据，所有表达刘易斯B或刘易斯y碳水化合物抗原的癌组织均为MSN-1阳性，表明其检测的抗原在癌症中显著增加，其表位可能是末端α-1，2岩藻糖基化碳水化合物残基，这在刘易斯B和刘易斯y之间是常见的。在本研究中，我们研究了MSN-1反应性抗原在子宫内膜腺癌标本中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。其次，采用RT-PCR方法比较了Se、H基因在癌组织和正常人乳腺组织中的表达，并检测了Se基因的错义突变，其纯合子（se/se）导致酶活性失活，从Se基因错义突变（se/se）患者中获得癌细胞。被MSN-1染色呈阳性。另一方面，mRNA来源于H基因，以及来自Se基因。在子宫内膜腺癌中的表达并不总是高于正常子宫内膜。此外，癌细胞表面的MSN-1反应性抗原与Se或刘易斯酶的mRNA表达均无相关性，提示子宫内膜癌特异性岩藻糖可能是由多种α-1，2岩藻糖基转移酶协同作用或由一种新的α-1，2岩藻糖基转移酶共同作用产生的。

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.