权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

INVOLVEMENT OF THE INACTIVATION OF DNA MISMATCH REPAIR SYSTEM ON THE CELLULAR IMMORTALIZATION MECHANISMS OF HUMAN GASTROINTESTINAL CANCERS.

DNA 错配修复系统失活对人类胃肠癌细胞永生化机制的影响。

基本信息

批准号：
14370070
负责人：
YOKOZAKI Hiroshi
金额：
$ 8.06万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

The purposes of the present research project were to clarify the mechanism of telomere maintenance, escapement mechanism from apoptosis through DNA mismatch repair defect and the rote of mismatch repair defect on the cellular immortalization of gastrointestinal cancers. The results obtained during the term were as following.Human gastric and colorectal cancers were subclassified according to the microsatellite status and p53 immunoreactivity as mutator-type (tumors with microsatellite instability (MSI)), suppressor/p53-type (mirosatellite stable (MSS) tumors with strong p53 expression or loss of heterozygosity at D17S250 (p53 locus) and unclassified (the other MSS tumors).1.Mutator-type gastric mucinous adenocarcinomas showed lower proliferative activity and better prognosis in comparison with other types. They also revealed the infrequent immunoreactivity to CD10, a marker for the brush-border of enterocytes. Mutator-type colorectal mucinous adenocarcinomas demonstrated significantly frequent immunoreaction to HGM, a gastric mucin marker, and had tendency to locate at proximal colon, while suppressor/p53-type tumors showed frequent venous infiltration and lymph node metastasis with higher clinicopathological stage. These indicated that mucinous carcinomas of the gastrointestinal tract might be subuclassified molecular pathologically.2.Infrequent expression of h TERT mRNA, a catalytic subunit of telomerase, was observed in mutator-type tumors in comparison with other subtypes when 208 cases of colorectal carcinomas were analyzed by in situ hybridization, suggesting that reactivation of telomerase might be a rare event in MSI colorectal carcinomas with telomerase independent cellular immortalization.3.A system for telomere length quantification on paraffin-embedded pathologrcal specimens was established during the term of the research project.

本研究旨在阐明端粒的维持机制、DNA错配修复缺陷对凋亡的逃逸机制以及错配修复缺陷在胃肠道肿瘤细胞永生化中的作用。本研究期内获得的结果如下：根据微卫星状态和p53免疫反应性将人胃癌和结直肠癌分为突变型（具有微卫星不稳定性（MSI）的肿瘤），抑制基因/p53型在D17 S250处具有强p53表达或杂合性缺失的微卫星稳定（MSS）肿瘤1.突变型胃粘液腺癌与其他类型胃粘液腺癌相比，增殖活性较低，预后较好。他们还揭示了对CD 10的罕见免疫反应性，CD 10是肠上皮细胞刷状缘的标志物。突变型结直肠粘液腺癌表现出明显频繁的免疫反应，HGM，胃粘蛋白标记物，并有倾向于位于近端结肠，而抑制/p53型肿瘤表现出频繁的静脉浸润和淋巴结转移，具有较高的临床病理分期。2.应用原位杂交技术检测了208例大肠癌组织中端粒酶催化亚单位hTERTmRNA的表达，发现突变型大肠癌中hTERTmRNA的表达较其他亚型少见，提示端粒酶再激活可能是MSI结直肠癌中端粒酶非依赖性细胞永生化的罕见事件。在研究期间建立了包埋的病理标本。