ANALYSIS OF TARGET GENES ACTIVATED--JUN ONCOPROTEIN

控制细胞生长调节的机制对于 对肿瘤发生的理解。这些机制包括信号链 会受到致癌基因的影响。为了分析这些机制， 人们必须了解癌基因的正常和异常功能，它们的靶点， 对细胞信号的影响。这项工作的长期目标是 深入了解致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 表征致癌重要的靶基因激活的 jun癌蛋白。这些知识对于理解 癌基因诱导细胞转化的过程以及 参与正常生长控制。 本研究将分为三个部分。第一个涉及 识别jun激活的主要靶基因。这将在 通过对随后立即产生的cDNA文库进行消减筛选， 针对未诱导文库诱导v-jun的表达。第二 区域涉及确定每个靶点的致癌潜力 鉴定这将通过测定细胞转化来进行， 由于潜在的大量靶标，这些试验将使用 DNA池转化阳性样本池中的重要靶标可以 解决问题第三个领域涉及的分子分析， 致癌重要的靶基因和结构和功能 他们的产品特征。

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.