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。

• 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

(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hMSH_2和hMLH_1的表达用本室研制的单克隆抗体，用Western blot方法检测了99例散发性大肠癌组织中hMSH_2和hMLH_1蛋白的表达。99例肿瘤组织中有11例hMSH 2（6例）和hMLH 1（5例）蛋白不表达或少量表达，表明约10%的散发病例存在这些错配修复蛋白的表达缺陷。(2)RER状态为了研究90例散发病例的RER状态，我们选择了5个微卫星标记。在90份样本中，有17份（18.9%）在微卫星区域有2个以上位点，其中11份hMLH 1或hMSH 2缺陷样本中有10份表现为RER表型。(3)靶基因的微卫星区域中的突变为了了解靶基因，研究了TGF-β RII、IGFIIR和BAX基因的微卫星区域中的突变。到目前为止，在15个RER样本中发现了TGF-β RII基因的一个等位基因突变。(4)未来的研究需要阐明用于确定日本患者RER状态的微卫星标记，因为没有常见的高频率微卫星标记用于检测RER。进一步的标本将检查RER状态和错配修复系统，包括靶基因的候选者。

项目成果

Koike J,Yamada K,Takano S., Kikuchi Y,Hemmi H,Koi M,Tsujita K,et al: "Undetectable expression of hMLH1 protein in sporadic colorectal cancew with replication error phenotype." Dis Colon Rect. 40. S23-S28 (1997)

Koike J、Yamada K、Takano S.、Kikuchi Y、Hemmi H、Koi M、Tsujita K 等人：“在具有复制错误表型的散发性结直肠癌中检测不到 hMLH1 蛋白的表达。”

Hemmi H,Kikuchi Y,Kato M,et al: "Expression of mismatch repair gene products, hMSH2 and hMLH1, by human neuroblastoma cell lines." Jpn J Pediat Oncol. 34. 23-27 (1997)

Hemmi H、Kikuchi Y、Kato M 等人：“人类神经母细胞瘤细胞系的错配修复基因产物 hMSH2 和 hMLH1 的表达。”

岩崎 匡洋: "散発性大腸癌におけるDNA修復遺伝子発現異常の解析" Vita. (印刷中). (1998)

Masahiro Iwasaki：“散发性结直肠癌中 DNA 修复基因表达异常的分析”Vita（1998 年出版）。

逸見仁道: "ヒト神経芽腫細胞株におけるミスマッチ修復遺伝子産物hMSH2及びhMLH1の発現" 小児がん. 34. 23-27 (1997)

Hitomi Itumi：“错配修复基因产物 hMSH2 和 hMLH1 在人神经母细胞瘤细胞系中的表达”小儿癌症。