NEOPLASTIC TRANSFORMATION BY RAS ONCOGENES

我们建议研究ras基因突变的分子基础， 癌基因引起肿瘤转化。 我们将利用 ras基因在进化过程中高度保守，我们将使用 果蝇作为模型系统来研究这个问题。 我们将在 在体外培养的果蝇ras基因中含有错义突变， 与导致人类出现肿瘤的氨基酸相同。 这 突变基因将通过P 元素介导的转化 我们认为这种显性突变 会在果蝇中产生肿瘤或其他一些可见的表型。 我们 将分离出能恢复这种表型的突变体 这个变种人会 要么逆转了ras基因的突变，要么将有一个新的 影响不同基因的突变，其蛋白质产物与 p21 ras编码蛋白。 然后我们将分离出这个基因， 蛋白质产品的生化和生理特性， 编码。 我们希望这些信息将有助于我们了解 p21在细胞生理学中的作用，以及其 氨基酸序列引起细胞转化。 （十）

We propose to investigate the molecular basis by which mutations in the ras oncogenes cause neoplastic transformation. We will take advantage of the high conservation of the ras genes during evolution and we will use Drosophila as a model system to study this problem. We will construct in vitro an altered Drosophila ras gene containing a missense mutation in the same amino acid that causes the appearance of tumors in humans. This mutant gene will be introduced into Drosophila embryos by P element-mediated transformation. We expect that this dominant mutation will give rise to tumors in the flies or some other visible phenotype. We will then isolate mutants that revert this phenotype. This mutant will either have reversed the mutation in the ras gene or will have a new mutation affecting a different gene whose protein product interacts with the p21 ras-encoded protein. We will then isolate this gene and study the biochemical and physiological characteristics of the protein product it encodes. We expect that this information will help us to understand the role of p21 in the physiology of the cell and how an alteration in its amino acid sequence gives rise to cell transformation. (X)