RETROVIRUSES AND CANCER GENES

正常细胞基因结构和功能的改变， 是致癌作用的核心 这项资助所支持的工作 旨在确定负责癌症生长的细胞基因， 致癌物质使这些基因发挥作用的方式，以及 基因的生化机制。 如果 搜索成功，它应该提供新的，更合理的， 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。 这项工作是在 主要是逆转录病毒， 代表了致癌作用的缩影 其中一些病毒 携带“癌基因”，直接将细胞转化为肿瘤 增长 其他逆转录病毒不具有致癌基因， 通过突变宿主细胞的DNA来诱发肿瘤。 两种形式的 逆转录病毒引起的肿瘤提供了获取细胞基因的途径， 可能有助于肿瘤生长： 逆转录病毒是正常细胞的完整拷贝的一部分， 基因（“原癌基因”），偶然地被转导入病毒 在评价过程中;和细胞的诱变 逆转录病毒的DNA激活基因，也可以被视为 原癌基因 使用了一套禽类逆转录病毒， 聚集，提供了实验模型，为大多数主要的 癌症的形式。 在这些病毒中， 癌基因（v-src、v-fps、v-myc、v-er B-B和v-myB）， 主要研究对象。 实验策略旨在 识别由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 正常的伪装;辨别其功能的变化， 解释肿瘤发生;识别细胞功能， 癌基因的反常参与了人类 肿瘤;并利用原癌基因的发现， 进行基因和生化分析， 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;纯化和化学分析 用重组DNA定点诱变;和 对黑腹果蝇和 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 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.