VIRUSES AND TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

这个项目的目标是阐明肿瘤的作用机制。 病毒，并确定自然引起的细胞变化 正在发生的人类恶性肿瘤。目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) 内源性逆转录病毒；(3)逆转录病毒的分子生物学 复制和转化；以及(4)所获知识的应用 从这些研究到寻找所涉及的原因和机制 人类的肿瘤转化。 在过去的一年里，我们的调查提供了重要的新的 对sis和ras基因的见解，以及对一个新的 人类癌基因，命名为DBL，来自弥漫性B细胞淋巴瘤。亮点 包括：展示正常人的表情 SIS/PDGF-2编码序列诱导细胞转化；多肽 猴肉瘤病毒v-sis转化基因产物的序列测定 (SSV)可分为四个区域，它们可能代表 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； 可能的细胞位置，其中的转化活动的 可能发挥SIS/PDGF-2蛋白的作用。关于RAS：三个人类RAS家庭 原癌基因被染色体定位；ras癌基因被检测到， 肺癌和乳腺癌中的克隆和至少部分特征 细胞系和尿路肿瘤；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。

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.