ROUS SARCOMA VIRUS: REPLICATION AND CELL TRANSFORMATION

正常细胞基因的结构和功能的变化在于 致癌的心脏。这笔赠款支持的工作旨在 识别负责癌细胞生长的细胞基因，方法是 哪些致癌物使这些基因发挥作用，以及生化 基因的作用机制。如果搜索成功，它应该 为预防、诊断和预防提供新的、更合理的策略 癌症的治疗；它还应该揭示正常的 细胞的生长和发育受到控制。这项工作已经完成 主要是逆转录病毒，其致瘤潜力代表着 致癌的缩影。其中一些病毒携带“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能 拥有癌基因，但却通过突变宿主的DNA来诱发肿瘤 细胞。逆转录病毒的两种肿瘤形成形式都提供了 可能促进肿瘤生长的细胞基因：癌基因 逆转录病毒是正常细胞基因的部分或全部拷贝。 (“原癌基因”)，意外地被转导到病毒在 进化过程；以及逆转录病毒对细胞DNA的突变 激活也可以被视为原癌基因的基因。一套 禽类逆转录病毒的使用，总的来说，提供了实验性的 大多数主要癌症的模型。这些病毒中有 代表五个癌基因(v-src、v-fps、v-myc、v-erb-B和v-myb) 是主要的研究对象。实验策略的目标是 鉴定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； 辨别它们功能的变化，这可能是肿瘤发生的原因； 鉴定与癌基因有关的细胞功能 在人类肿瘤的起源方面；并利用发现 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； 多克隆抗体和单抗的制备； 免疫沉淀；免疫荧光和电子显微镜； 蛋白质的提纯和化学分析.定点突变 以及对果蝇和黑腹果蝇的遗传分析 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.