RETROVIRUSES AND CANCER GENES

正常细胞基因的结构和功能的变化 处于致癌的核心。由这笔赠款支持的工作 试图找出导致癌细胞生长的细胞基因， 致癌物使这些基因发挥作用的方式，以及 基因发挥作用的生化机制。如果 搜索成功，应该提供新的、更理性的 预防、诊断和治疗癌症的策略；以及 它还应该揭示正常增长和 细胞的发育受到控制。这项工作已经完成 主要是逆转录病毒，它的致瘤潜力 代表了癌症发生的一个缩影。其中一些病毒 携带可直接将细胞转化为肿瘤的“癌基因” 成长。其他逆转录病毒不具有癌基因，而是 通过突变宿主细胞的DNA来诱发肿瘤。这两种形式的 逆转录病毒的肿瘤形成提供了接触细胞基因的途径 可能对肿瘤生长有贡献：癌基因 逆转录病毒是正常细胞的部分完整拷贝。 基因(“原癌基因”)，意外地转入病毒 在评估过程中；以及细胞的诱变 逆转录病毒的DNA激活的基因也可以被认为是 原癌基因。一套禽类逆转录病毒被用来在 Aggregate，为大多数主要的 各种形式的癌症。在这些病毒中，有五种 癌基因(v-src、v-fps、v-myc、v-erb-B和v-myb) 主要研究对象。实验策略的目标是 鉴定癌基因和原癌基因编码的蛋白质 癌基因；确定这些蛋白质在其 正常的外表；他们的功能有可能发生明显的变化 解释肿瘤的发生；鉴定其细胞功能 癌基因的变态与人类的起源有关 肿瘤；以及利用原癌基因的发现来 进行遗传和生物化学分析，以了解生长和 正常细胞的分化受到控制。方法包括 分子克隆；核苷酸测序；DNA介导的基因 转移；多克隆和单克隆的制备 抗体；免疫沉淀；免疫荧光和 电子显微镜.提纯和化学分析 蛋白质；用重组DNA进行定点突变；以及 黑腹果蝇和黑腹果蝇的遗传分析 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 of complete copies of normal cellular genes ("proto-oncogenes"), transduced into the viruses by accident during the course of evaluation; 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 DNA; and genetic analyses with both Drosophila melanogaster and Saccharomyces cerevisiae.