ISOLATION OF TUMOR SUPPRESSOR GENE ON CHROMOSOME 3P

3P染色体上抑癌基因的分离

• 批准号: 2882386
• 负责人: SUSAN L NAYLOR
• 金额: $ 26.28万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882386
• 关键词: animal genetic material tag; antineoplastics; apoptosis; athymic mouse; chromosome deletion; complementary DNA; drug interactions; gene interaction; genetic mapping; human tissue; immunoprecipitation; in situ hybridization; laboratory rabbit; lung neoplasms; methylation; molecular cloning; neoplasm /cancer genetics; neoplastic transformation; northern blottings; nucleic acid sequence; polymerase chain reaction; restriction mapping; single strand conformation polymorphism; small cell lung cancer; southern blotting; tumor suppressor genes

The short arm of human chromosome 3 in the region 3p21.3 is deleted in many cancers including lung cancer which is the cause of 40,000 deaths in the U.S. each year. A fragment of chromosome 3 from this region suppresses tumor formation of A9 mouse fibrosarcoma cells in a nude mouse assay. Furthermore, this same fragment of chromosome 3 changes the response of A9 cells to chemotherapeutic drugs from apoptosis to growth arrest. This study is designed to identify the gene inducing tumor suppression in A9 and to determine whether it is the same gene imparting the differential response to chemotherapeutic drugs. The cDNA which suppresses tumor growth of mouse A9 fibrosarcoma cells will be identified using an inducible expression system. The candidate cDNA will be tested to determine if it is the same gene which gives a differential response to chemotherapeutic drugs. The cDNA which induces tumor suppression and differential drug response in mouse A9 cells will be tested for these effects in human tumor cells including small call lung cancer. The inactivation of this gene in human tumors will be explored by both mutation analysis and by methylation assays. The mechanism of action of the tumor suppressor gene and the basis of the switch from apoptosis to growth arrest will be determined relating this gene to other genes in apoptotic pathways. This study will define a gene which already has been implicated in a number of cancers by deletion and define its functioning in normal cells and during tumorigenesis. Status of this gene in a tumor may provide clues about that tumor's response to chemotherapeutic drugs.

人类3号染色体3p21.3区域的短臂在2010年缺失。 包括肺癌在内的许多癌症导致了4万人死亡 在美国每年。 3号染色体的一个片段 抑制A9小鼠纤维肉瘤细胞在裸鼠体内的肿瘤形成 小鼠试验 此外，3号染色体的同一片段 A9细胞对化疗药物的反应从凋亡到凋亡， 生长停滞 本研究的目的是鉴定诱导 A9中的肿瘤抑制，并确定其是否是相同的基因 赋予对化疗药物的不同反应。 的cDNA 抑制小鼠A9纤维肉瘤细胞的肿瘤生长， 使用诱导型表达系统鉴定。 候选cDNA 将进行测试，以确定它是否是相同的基因，使一个 对化疗药物的不同反应。 能够诱导 小鼠A9细胞中的肿瘤抑制和不同的药物反应将 在人类肿瘤细胞中测试这些作用，包括小细胞肺癌。 肺癌 这种基因在人类肿瘤中的失活， 通过突变分析和甲基化测定来探索。 的 肿瘤抑制基因的作用机制和基础 将确定从凋亡到生长停滞转换 基因与其他基因在凋亡途径中的相互作用。 本研究将定义一个 该基因已经与多种癌症有关， 删除并定义其在正常细胞中的功能， 肿瘤发生 这种基因在肿瘤中的状态可以提供线索， 肿瘤对化疗药物的反应