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: 3916745
• 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/3916745
• 关键词: Retroviridae; Retroviridae disease; breast neoplasms; deoxyribonucleotides; epidermal growth factor; growth factor receptors; human immunodeficiency virus 1; human tissue; lymphoma; molecular oncology; neoplasm /cancer genetics; neoplastic transformation; nucleic acid sequence; oncogenes; oncogenic virus; oncoproteins; protein kinase C; reverse transcriptase inhibitors; transforming growth factors; transforming virus; viral carcinogenesis; viral leukemogenesis; virus DNA; virus RNA; virus genetics; virus replication

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.

该项目的目标是阐明作用机制 并确定细胞的变化 导致自然发生的恶性肿瘤 议题 目前的研究热点包括：（1）逆转录病毒的转化基因 （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应用于 研究人类疾病的原因和机制， 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）基因被发现是经常 在人恶性肿瘤中扩增和/或过表达。 高水平 EGFR表达，这赋予了一个转化的表型， NIH/3 T3细胞在配体的存在下，在人 含有EGFR基因扩增拷贝的肿瘤细胞系。 (2)人erbB-2基因可被激活为癌基因， 在NIH/3 T3细胞中过表达。 高水平的erbB-2 NIH/3 T3细胞恶性转化相关产物 在过表达这种蛋白的人乳腺肿瘤细胞中观察到 基因 这些发现证明了一种新的获取机制 生长因子受体编码基因的致癌特性- 比如蛋白质。 (3)ras基因编码的p21蛋白可能与p21蛋白的表达有关。 作为信号转导的调节蛋白， DNA合成 (4)DBL转化基因产物，分离 从人类B细胞淋巴瘤，被证明是不同的， 已知的转化基因产物。 (4)的作用机制 显著抑制慢病毒的双脱氧核苷 感染性，进一步表征。