Generation of gastrointestinal cancers by abnormal mismatch repair system : Analysis mainly focused in target genes.

异常错配修复系统产生胃肠癌：分析主要集中在目标基因。

基本信息

批准号：
08671488
负责人：
HEMMI Hiromichi
金额：
$ 1.41万
依托单位：
TOHO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671488/
关键词：
mismatch repair genes hMLH1 protein hMSH2 protein RER microsatellite instability target genes TGF-beta signaling pathway BAX gene hMLHタンパク hMLH1遺伝子 TGF-βRII遺伝子 IGFIIR遺伝子

项目摘要

(1) Expression of mismatch repair proteins, hMSH2 and hMLHl Expression of hMSH2 and hMLH1 proteins in 99 samples of sporadic colorectal cancer selected ramdomly was analyzed by Western blot with monoclonal antibodies developed in our laboratory. Totally 11 samples with no/little expressing hMSH2 (6 samples) and hMLH1 (5 samples) proteins in 99 tumor tissues were found, indicating approximately l0% of sporadic cases have some defects in the expression of these mismatch repair proteins.(2) RER status To study RER status of the 90 sporadic cases, we selected 5 microsatellite markers. So far, l7 samples showing more than 2 loci of the microsatellite region of the 90 samples (l8.9%) were found. Ten of the 11 hMLH1- or hMSH2-defective samples showed RER phenotype.(3) Mutation in microsatellite region of target genes To know the target genes, mutation in the microsatellite regions of the TGF-betaRII,IGFIIR,and BAX genes were studied. So far, mutation in one allele of the TGF-betaRII genes of the 15 RER samples was found.(4) Future study lt is required to clarify the microsatellite markers for determining the RER status for Japanese patients, because there is no common microsatellite markers with high frequency for the detecting RER.Further specimens will be examined for RER status and mismatch repair system including candidates of target genes.

(1)错配修复蛋白、hMSH2和hMLH1的表达随机选取99例散发性结直肠癌样本，用本实验室研制的单克隆抗体进行Western blot分析hMSH2和hMLH1蛋白的表达。在99个肿瘤组织中，共发现11个样本无/少表达hMSH2（6个样本）和hMLH1（5个样本）蛋白，表明大约10％的散发病例存在这些错配修复蛋白表达的缺陷。（2）RER为了研究 90 例散发病例的 RER 状态，我们选择了 5 个微卫星标记。至此，90个样本中发现l7个样本显示微卫星区2个以上位点（l8.9%）。 11个hMLH1或hMSH2缺陷样品中有10个显示RER表型。(3)靶基因微卫星区突变为了了解靶基因，对TGF-betaRII、IGFIIR和BAX基因的微卫星区突变进行了研究。目前已发现15个RER样本的TGF-betaRII基因的一个等位基因发生突变。(4)未来的研究需要明确确定日本患者RER状态的微卫星标记，因为没有通用的微卫星标记高频率地检测RER。将检查更多样本的RER状态和错配修复系统，包括候选目标基因。