VIRUSES AND TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

这个项目的目标是阐明其作用机制。 并确定细胞的变化 对自然发生的恶性肿瘤负责。主题： 目前的兴趣包括：(1)逆转录病毒的基因转化 和癌细胞：(2)内源性逆转录病毒的生物学：(3) 逆转录病毒复制和转化的分子生物学： 以及(4)将从这些研究中获得的知识用于 人类致病原因和致病机制的探索 肿瘤性转化。 过去一年的一些亮点包括：(1)表皮 生长因子受体(EGFR)基因是一种常见的 在人类恶性肿瘤中扩增和/或过度表达。高水平 EGFR的表达，这使得转化的表型 在人NIH/3T3细胞中发现了配体的存在 含有EGFR基因扩增拷贝的肿瘤细胞系。 (2)人类erbB-2基因可被其激活为癌基因。 在NIH/3T3细胞中过表达。高水平的erbB-2 与NIH/3T3细胞恶性转化相关的产物 在过度表达该基因的人乳腺肿瘤细胞中观察到 吉恩。这些发现证明了一种新的收购机制 通过编码生长因子受体的基因的致癌特性- 像蛋白质一样。(3)ras基因编码的p21蛋白可能起作用。 作为调节蛋白在信号转导中导致 DNA合成。(4)分离的DBL转化基因产物 从人类B细胞淋巴瘤中分离出来的，被证明与 已知的转化基因产品。(四)作用机制。 能显著抑制慢病毒的双脱氧核苷 传染性，进一步表征了其传染性。

The goals of this project are to elucidate the mechanisms of action of tumor viruses and to determine the cellular alterations responsible for naturally occurring 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. Some of the highlights of the past year include: (1) The epidermal growth factor receptor (EGFR) gene was found to be frequently amplified and/or overexpressed in human malignancies. High levels of EGFR expression, which conferred a transformed phenotype to NIH/3T3 cells in the presence of ligand, were demonstrated in human tumor cell lines that contained amplified copies of the EGFR gene. (2) The human erbB-2 gene can be activated as an oncogene by its overexpression in NIH/3T3 cells. The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene. These findings demonstrate a new mechanism for acquisition of oncogenic properties by genes encoding growth factor receptor- like proteins. (3) The p21 proteins encoded by ras genes may act as regulatory proteins in the transduction of signals that lead to DNA synthesis. (4) The dbl transforming gene product, isolated from a human B-cell lymphoma, was demonstrated to be distinct among known transforming gene products. (4) The mechanism of action of the dideoxynucleosides, which markedly inhibit lentivirus infectivity, was further characterized.