VIRUSES AND TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

实验性癌发生和人类癌症中的病毒和转化基因

• 批准号: 4692302
• 负责人: S A AARONSON
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4692302
• 关键词: Burkitt's lymphoma; Retroviridae; breast neoplasms; cancer prevention; cellular oncology; chromosome translocation; clone cells; cocarcinogen; electron microscopy; feline leukemia /sarcoma virus; gene expression; genetic mapping; human tissue; immunologic techniques; lymphoma; molecular oncology; mouse sarcoma virus; neoplasm /cancer genetics; nucleic acid sequence; oncogenes; oncogenic virus; radioimmunoassay; transforming virus; viral carcinogenesis; virus DNA; virus RNA; virus classification; virus genetics; virus replication

The goals of this project are to elucidate the machinsms of action of tumor viruses and to determine the cellular alterations responsible for naturally occurring human malignancies. topics of present interest include: (1) transforming genes of retroviruses and cancer cells; (2) the biology of endogenous retroviruses; (3) the molecular biology of retrovirus replication and transformation; and (4) the application of knowledge gained from these studies to the search for the causes and mechanisms involved in human neoplastic transformation. During the past year, our investigations have provided important new insights regarding sis and ras genes, as well as indentification of a new human oncogene, designated dbl, from a diffuse B cell lymphoma. Highlights of sis include: demonstration that expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation; the polypeptide sequence of the v-sis transforming gene product of simian sarcoma virus (SSV) is divisible into four regions which are likely to represent structural domains of the protein; the v-sis transforming gene encodes the woolly monkey homologue of human PDGE polypeptide 2; and definition of possible cellular locations where the transforming activity of the sis/PDGF-2 protein may be exerted. Regarding ras: three human ras family protooncogenes were chromosomally mapped; ras oncogenes were detected, cloned and at least partially characterized in lung and mammary carcinoma cell lines, as well as tumors of the urinary tract; activation of ras oncognees in human tumors appears to be most commonly due to point mutations at one of two major "hot spots" (codons 12 and 61) in the ras coding sequence.

本项目的目标是阐明肿瘤的作用机制， 病毒，并确定细胞的变化，负责自然 发生人类恶性肿瘤。 当前感兴趣的主题包括：（1） 逆转录病毒和癌细胞的转化基因;（2） 逆转录病毒的分子生物学 复制和转化;（4）应用获得的知识 从这些研究到寻找参与的原因和机制， 人类肿瘤转化 在过去的一年里，我们的调查提供了重要的新信息， 关于sis和ras基因的见解，以及新的 来自弥漫性B细胞淋巴瘤的人癌基因，命名为db 1。 亮点 SIS包括：正常人表达展示 sis/PDGF-2编码序列诱导细胞转化;所述多肽 猿猴肉瘤病毒的v-sis转化基因产物的序列 (SSV)可分为四个区域， 蛋白质的结构域; v-sis转化基因编码 人PDGE多肽2的毛猴同源物;以及 可能的细胞位置， 可以发挥sis/PDGF-2蛋白。 关于ras：三个人类ras家族 对原癌基因进行染色体定位;检测ras癌基因， 在肺癌和乳腺癌中克隆并至少部分表征 细胞系以及泌尿道肿瘤; ras的激活 人类肿瘤中的肿瘤似乎最常见的原因是 ras中两个主要“热点”（密码子12和61）之一的突变 编码序列