Analysis of gene alterations associated with endometrial cancers and the target of the gene therapy

子宫内膜癌相关基因改变分析及基因治疗靶点

• 批准号: 06454473
• 负责人: INOUE Masaki
• 金额: $ 4.16万
• 依托单位: Kanazawa University (1995-1996)Osaka University (1994)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454473/
• 关键词: Gynecologic cancer; Oncogene; Anti-oncogenes; DNA repair genes; Telomerase; Gene therapy; Endometrial cancer; Multistep carcinogenesis; 細胞の不死化; 遺伝子治療; テロメラーゼ; 子宮癌; prot on cogene; anti-oncogene; multistep carcinoglvesis; p53; Rb; DCC; HD

Recent advances in molecular biology have allowed us to study cancer at the level of individual genes. Such works have led to the theory of multistep carcinogenesis.The present study showed that activation of oncogenes, inactivation of tumor-suppresor genes, inactivation of mismatched-DNA repair genes and infection of human papillomavirus were closely involved in the carcinogenesis of uterine endometrium. Alterations of Ras, p53, DCC,P16, C-kit/SCF,RB were totally found in 17/26 (65%) G1 adenocarcinmas, 5/7 (71%) G2 adenocarcinomas and 12/13 (92%) G3 adenocarcinomas. However, the each abnormality of a single gene is quite low in its incidence.A frequent genetic change which takes place in carcinogenesis should be choosed as the target molecule of gene therapy. Our modified non-Rl TRAP (telomeric repeat amplification protocol) assay found that the telomerase activation was common (more than 90%) in endometrial cancer and was a critical step in their pathogenesis. Then, in the present time, the best target of gene therapy might be a telomerase molecule.

分子生物学的最新进展使我们能够在单个基因水平上研究癌症。这样的工作导致了多步癌发生的理论。目前的研究表明，癌基因的激活，肿瘤辅助基因失活，不匹配的DNA修复基因失活以及人乳头瘤病毒的感染与子宫心脏trimentrium的癌变相关。 RAS，p53，DCC，P16，C-KIT/SCF，RB的变化在17/26（65％）G1 adenocarcinmas，5/7（71％）G2 G2 adenocarcinomas和12/13（92％）G3 adenocarcinomas中的变化。然而，单个基因的发病率都很低。癌变中发生的频繁遗传变化应作为基因治疗的靶标分子。我们修饰的非RL陷阱（端粒重复扩增方案）测定法发现，子宫内膜癌中端粒酶的激活是常见的（超过90％），并且是其发病机理的关键步骤。然后，目前，基因治疗的最佳靶标可能是端粒酶分子。

项目成果

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Kyo S 等人：“妇科肿瘤中的端粒酶活性。”

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Enomoto T 等人：“子宫内膜样腺癌中 p53 肿瘤抑制基因的改变和 c-K-ras-2 原癌基因的激活：来自美国科罗拉多州和日本大阪的样本之间的比较”Am J Clin Pathol。