Relationship between genetic abnormalities of cell cycle regulators and genetic and chromosomal instabilities in gastrointestinal carcinomas

细胞周期调节因子的遗传异常与胃肠癌遗传和染色体不稳定性的关系

• 批准号: 08670204
• 负责人: YASUI Watartu
• 金额: $ 1.47万
• 依托单位: HIROSHIMA 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 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670204/
• 关键词: Gastrointestinal carcinoma; Cell cycle regulators; Genetic instability; Telomerase; TERT; CyclinE; p27; E2F-1; CDKインヒビター

1. Genetic and chromosomal instabilities in gastrointestinal carcinomasGenetic instability (replication error : PER) was examined in the gastric carcinomas by microsatellite analysis, and was found in 30% of the cases. Especially, the instability at D 17S855 locus (near BRCA1) was frequent in younger patients. RER was also detected in a part of intestinal metaplasia next to gastric carcinoma. RER at more than two of the four loci was found in 3% of the gastric carcinomas, a half of which had multiple primary cancers.Strong telomerase activity and increased hTR expression were detected in most of the gastric carcinomas and a portion of precancerous lesions. The telomerase activities were well correlated with the levels of TERT expression in most of the gastric and colorectal carcinomas. TERT expression was also detected in some of the adenomas and intestinal metaplasia of the stomach.2. Genetic abnormalities of cell cycle regulators in gastrointestinal carcinomasGene amplification and o … More verexpression of cyclin E occurred frequently in the gastric and colorectal carcinomas that was closely related with high grade malignancy. About 70% of the gastric carcinomas expressed CDC25B at high levels. Reduced expression of p27, a CDK inhibitor, correlated well with aggressive behavior (advanced tumor stage, deeply invasion, and lymph-node metastasis) of the gastric and colorectal carcinomas. Gene amplification of E2F-1, an important target molecule of cell cycle regulators, was detected in 4% and 25% of the gastric and colorectal carcinomas, respectively. About 40% of the gastric carcinomas overexpressed E2F-1 mRNA.On the other hand, the expression of E2F-3 was reduced in 70% of the gastric carcinomas.3. Relationship between telomerase and cell cycle regulatorsRelationship between telomerase activity and the expression of various cyclins and CDK inhibitors in the gastric carcinomas. The expression of cyclin E tended to correlate with the telomerase activity, while no obvious tendency was detected between telomerase and the expression of p21 and p27. Less

1.胃肠道肿瘤的遗传和染色体不稳定性用微卫星分析法检测了胃癌中的遗传不稳定性（复制错误：PER），发现在30%的病例中存在。尤其是D17 S855位点（BRCA 1附近）的不稳定性在年轻患者中更常见。癌旁部分肠上皮化生组织中也可见粗面内质网。在40例胃癌中，RER在2个以上位点的阳性率为3%，其中半数为多原发癌，端粒酶活性和hTR表达在大多数胃癌和部分癌前病变中呈强阳性。大多数胃癌和结直肠癌组织中端粒酶活性与端粒酶逆转录酶的表达水平呈正相关。在部分胃腺瘤和肠上皮化生中也检测到TERT的表达.胃肠道肿瘤细胞周期调控因子基因异常的研究 ...更多信息 cyclin E在胃癌和结直肠癌中的高表达与高度恶性密切相关。约70%的胃癌组织高表达CDC 25 B。CDK抑制剂p27的表达降低与胃癌和结直肠癌的侵袭行为（晚期肿瘤分期、深度浸润和淋巴结转移）密切相关。E2 F-1是细胞周期调控的重要靶分子，其基因扩增分别在4%和25%的胃癌和结直肠癌中检测到。约40%的胃癌组织中E2 F-1 mRNA过表达，70%的胃癌组织中E2 F-3 mRNA表达降低.端粒酶与细胞周期调控因子的关系胃癌中端粒酶活性与细胞周期蛋白和细胞周期蛋白激酶抑制因子表达的关系细胞周期蛋白E的表达与端粒酶活性有相关性，而端粒酶活性与p21、p27的表达无明显相关性。少

项目成果

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Akagi M：“转化生长因子β对细胞生长的抑制与胃癌细胞中p53独立的p21诱导有关”，日本癌症研究杂志87·4（1996）。

Kitadai Y: "Expression of IL-8 correlates with vascularity in human gastric carcinomas" American Journal of Pathology. 152・1. 93-100 (1998)

Kitadai Y：“IL-8 的表达与人类胃癌中的血管分布相关”美国病理学杂志 152・1（1998）。

Yamamoto S: "Expression of vascular endothelial growth factor in human gastric carcinomas" Pathology International. 48・7. 499-506 (1998)

Yamamoto S：“血管内皮生长因子在人胃癌中的表达”病理学国际48·7（1998）。

Ito R: "Growth stimulatory effect of interleukin (IL) -la produced by oral squamous cell carcinoma cell limes" Int J Oncol. 11(4). 807-812 (1997)

Ito R：“口腔鳞状细胞癌细胞莱姆产生的白细胞介素 (IL) -la 的生长刺激作用”Int J Oncol。

Yasui W: "Expression of telomerase catalytic component, telomerase reverse transcriptase, in human gastric carcinomas" Jpn J Cancer Res. 89(11). 1099-1103 (1998)

Yasui W：“端粒酶催化成分、端粒酶逆转录酶在人胃癌中的表达”Jpn J Cancer Res。