ROUS SARCOMA VIRUS: REPLICATION AND CELL TRANSFORMATION

正常细胞基因结构和功能的改变， 致癌的核心 这项赠款支持的工作旨在 确定负责癌生长的细胞基因， 哪些致癌物质会使这些基因发挥作用， 基因的作用机制。 如果搜索成功， 提供新的和更合理的战略，预防，诊断和 癌症的治疗;它也应该揭示的原则， 细胞的生长和发育受到控制。 这项工作是在 主要是逆转录病毒，其致瘤潜力代表了 癌症发生的缩影 其中一些病毒携带的“致癌基因”， 直接将细胞转化为肿瘤生长。 其他逆转录病毒则不 具有致癌基因，但通过突变宿主的DNA而诱发肿瘤 细胞 逆转录病毒引起的两种形式的肿瘤发生都提供了进入 可能有助于肿瘤生长的细胞基因： 逆转录病毒是正常细胞基因的部分或完整拷贝 （“原癌基因”），在病毒传播过程中偶然被导入病毒。 进化过程;逆转录病毒对细胞DNA的诱变 激活也可被视为原癌基因的基因。 一套 使用禽类逆转录病毒，其总体上提供实验性的 大多数主要癌症的模型。 在这些病毒中， 代表五种癌基因（v-src、v-fps、v-myc、v-er B-B和v-myB）， 是主要的研究对象。 实验策略旨在 鉴定由癌基因和原癌基因编码的蛋白质; 确定这些蛋白质在正常情况下的功能; 识别可能导致肿瘤发生的功能变化; 鉴定与癌基因的反常有关的细胞功能 在人类肿瘤的发生中， 原癌基因进行遗传和生化分析， 正常细胞的生长和分化受到控制。 方法包括 分子克隆;核苷酸测序; DNA介导的基因转移; 制备多克隆和单克隆抗体; 免疫沉淀;免疫荧光和电子显微镜; 蛋白质的纯化和化学分析;定点突变 与重组;和遗传分析与果蝇黑腹 和酿酒酵母。

Changes in the structure and function of normal cellular genes lie at the heart of carcinogenesis. The work supported by this grant seeks to identify cellular genes responsible for cancerous growth, the means by which carcinogens bring these genes into play, and the biochemical mechanisms by which the genes act. If the search succeeds, it should provide new and more rational strategies for the prevention, diagnosis and therapy of cancer; and it should also reveal principles by which the normal growth and development of cells are controlled. The work is conducted primarily with retroviruses, whose tumorigenic potentials represent a microcosm of carcinogenesis. Some of these viruses carry "oncogenes" that directly convert cells to neoplastic growth. Other retroviruses do not possess oncogenes but instead induce tumors by mutating the DNA of host cells. Both forms of tumorigenesis by retroviruses offer access to cellular genes that may contribute to neoplastic growth: the oncogene of retroviruses are partial or complete copies of normal cellular genes ("proto-oncogenes"), tranduced into the viruses by accident during the course of evolution; and the mutagenesis of cellular DNA by retroviruses activates genes that can also be regarded as proto-oncogenes. A suite of avian retroviruses is used that, in the aggregate, provides experimental models for most of the major forms of cancer. Among these viruses are represented five oncogenes (v-src, v-fps, v-myc, v-erb-B, and v-myb) that are major objects of study. Experimental strategies are aimed at identifying the proteins encoded by oncogenes and proto-oncogenes; determining the functions of these proteins in their normal guise; discerning changes in their function that may account for tumorigenesis; identifying cellular functions whose perversion by oncogenes are involved in the genesis of human tumors; and exploiting the discovery of proto-oncogenes to perform genetic and biochemical analyses of how the growth and differentiation of normal cells is controlled. Methods include molecular cloning; nucleotide sequencing; DNA-mediated gene transfer; preparation of both polyclonal and monoclonal antibodies; immunoprecipitation; immunofluorescence and electron microscopy; purification and chemical analysis of proteins; site-directed mutagenesis with recombinant; and genetic analyses with both Drosophila melanogaster and Saccharomyces cerevisiae.