The role of inhibitory transcription factor GCF on invasion and metastasis of gastrointestinal cancer and its genetic abnormality

抑制性转录因子GCF在胃肠道肿瘤侵袭转移及遗传异常中的作用

• 批准号: 06670192
• 负责人: YASUI Wataru
• 金额: $ 1.22万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670192/
• 关键词: Inhibitory Transcription Factor; Gastrointestinal Cancer; Invasion; Metastasis; Genetic Abnormality; Cell Adhesion Molecule; Growth Factor; GCF

1. The role of GCF in invasion and metastasis of gastrointestinal cancerThe expression vector of GCF gene was introduced gastric carcinoma cell lines and stable cell lines with GCF overexpression were established. In vitro growth was suppressed and tumorigenicity was reduced by GCF overexpression. However, both control cells and GCF-transfectants did not show metastatic ability. The levels of GCF in gastric carcinoma cell lines showed tendency to correlate with the expression and secretion of vascular endothelial growth factor (VEGF) which participates in tumor invasion and metastasis through angiogenesis. GCF did not affect the induction of VEGF by EGF in these cell lines.2.Genetic abnormality of GCFGenetic instability on GCF gene locus (D2S110, chromosome 2q14) was examined in gastric carcinomas and precancerous lesions by microsatellite analysis Replication error (RER (+) ) was detected in 17% of gastric carcinmas, many of which also showed RER in different loci such as D2S123 and D2S136. RER (+) of GCF gene locus was detected in 18% of gastric adenomas and none of intestinal metaplasia. This genetic instability may cause loss of GCF function, resulting in overexpression of several genes related to proliferation and progression.3. Molecular mechanism of invasion and metastasis of gastrointestinal cancerIt was found that cadherin-catenin system, beta1-integrin and 31kDa lactoside-binding lectin participate in invasion and metastasis of gastric carcinomas. HGF enhanced motility and scattering of gastric carcinoma cells, while HGF reduced the expression of E-and P-cadherin. The amplification and overexpression of cyclin E was associated with invasion and metastasis of gastric and colorectal carcinomas.

1、GCF在胃肠道肿瘤侵袭转移中的作用导入GCF基因表达载体的胃癌细胞系，建立GCF过表达的稳定细胞系。 GCF 过表达可抑制体外生长并降低致瘤性。然而，对照细胞和GCF转染子均未表现出转移能力。胃癌细胞系中GCF的水平与血管内皮生长因子（VEGF）的表达和分泌呈相关性，VEGF通过血管生成参与肿瘤的侵袭和转移。 GCF不影响EGF在这些细胞系中诱导VEGF。2.GCF的遗传异常通过微卫星分析在胃癌和癌前病变中检查GCF基因位点（D2S110，染色体2q14）的遗传不稳定性在17％的胃癌中检测到复制错误（RER（+）），其中许多也显示 RER 位于不同位点，例如 D2S123 和 D2S136。 18%的胃腺瘤中检测到GCF基因位点RER（+），而肠化生中没有检测到。这种遗传不稳定性可能导致GCF功能丧失，导致与增殖和进展相关的多个基因过度表达。3．胃肠癌侵袭和转移的分子机制研究发现钙粘蛋白-连环蛋白系统、β1-整合素和31kDa乳糖苷结合凝集素参与胃癌的侵袭和转移。 HGF增强胃癌细胞的运动性和分散性，同时HGF降低E-和P-钙粘蛋白的表达。 cyclin E的扩增和过表达与胃癌和结直肠癌的侵袭和转移有关。

项目成果

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