ISOLATION OF TUMOR SUPPRESSOR GENE ON CHROMOSOME 3P

3P染色体上抑癌基因的分离

• 批准号: 6164078
• 负责人: SUSAN L NAYLOR
• 金额: $ 26.9万
• 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/6164078
• 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 区域的短臂被删除 许多癌症，包括肺癌，导致 40,000 人死亡 每年在美国。 来自该区域的 3 号染色体片段 抑制裸鼠 A9 小鼠纤维肉瘤细胞的肿瘤形成 小鼠测定。 此外，3 号染色体的同一片段也发生了变化 A9细胞对化疗药物的反应从凋亡到 生长停滞。 本研究旨在鉴定诱导基因 A9中的肿瘤抑制并确定是否是同一基因 赋予化疗药物不同的反应。 cDNA 抑制小鼠 A9 纤维肉瘤细胞的肿瘤生长 使用诱导表达系统进行鉴定。 候选cDNA 将进行测试以确定它是否是相同的基因 对化疗药物的不同反应。 诱导的cDNA 小鼠 A9 细胞的肿瘤抑制和差异药物反应将 在人类肿瘤细胞（包括小细胞）中测试这些效应 肺癌。 该基因在人类肿瘤中的失活将是 通过突变分析和甲基化测定进行探索。 这 抑癌基因的作用机制及基础 从细胞凋亡到生长停滞的转变将被确定与此相关 细胞凋亡途径中的基因与其他基因的关系。 这项研究将定义一个 该基因已被证实与多种癌症有关 删除并定义其在正常细胞中和期间的功能 肿瘤发生。 该基因在肿瘤中的状态可能提供以下线索： 肿瘤对化疗药物的反应。