ANALYSIS OF TARGET GENES ACTIVATED--JUN ONCOPROTEIN

激活靶基因分析--JUN ONCOPROTEIN

• 批准号: 3459836
• 负责人: TIMOTHY J BOS
• 金额: $ 8.91万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3459836
• 关键词: cell growth regulation; cytogenetics; gene conversion; gene expression; gene mutation; genetic library; genetic regulatory element; genetic transcription; laboratory rabbit; oncogenes; structural genes; transcription factor

The mechanisms governing the regulation of cell growth are fundamental to the understanding of tumorigenesis. These mechanisms include signal chains that can be affected by oncogenes. In order to analyze these mechanisms, one must know normal and aberrant functions of oncogenes, their targets and effects on cellular signalling. The long term objective of this work is to gain insight into the mechanisms by which oncogenes turn normal cells into cancer cells. The specific aims focus on the identification and molecular characterization of oncogenically important target genes activated by the jun oncoprotein. This knowledge will be invaluable in understanding the process by which oncogenes induce cell transformation as well as the steps involved in normal growth control. This study will be divided into three parts. The first involves the identification of primary target genes activated by jun. This will be done by subtraction screening of a cDNA library generated immediately after induction of expression of v-jun, against an uninduced library. The second area involves the determination of oncogenic potential of each target identified. This will be performed by assaying for cell transformation in the potential large number of targets, these assays will be performed with pools of DNA. Important targets from transformation positive pools can then be sorted out. The third area deals with a molecular analysis of oncogenically important target gene(s) and a structural and functional characterization of their products.

调控细胞生长的机制是 对肿瘤发生的理解。这些机制包括信号链 这可能会受到癌基因的影响。为了分析这些机制， 人们必须知道癌基因的正常和异常功能，它们的靶点和 对细胞信号的影响。这项工作的长期目标是 深入了解癌基因将正常细胞转化为 癌细胞。具体目标集中在鉴定和分子水平上。 致癌重要靶基因的特性研究 Jun癌蛋白。这些知识将对理解 癌基因诱导细胞转化的过程和步骤 参与正常的生长控制。 本研究将分为三个部分。第一个问题涉及 Jun激活的主要靶基因的鉴定。这件事会做到的 通过消减筛选紧随其后产生的cDNA文库 针对未诱导的文库，诱导v-jun的表达。第二 区域涉及每个目标的致癌潜力的确定 确认身份。这将通过检测细胞转化来执行 潜在的大量目标，这些分析将与 DNA池。然后，来自转型积极池的重要目标可以 被理清头绪。第三个领域涉及分子分析 致癌重要靶基因(S)及其结构和功能 对他们的产品进行表征。