ERB-B ACTIVATION: FROM EGF-RECEPTOR TO LEUKEMIA ONCOGENE

ERB-B 激活：从 EGF 受体到白血病癌基因

• 批准号: 3079705
• 负责人: ROBERT J PELLEY
• 金额: $ 7.47万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079705
• 关键词: DNA; Retroviridae disease; avian leukosis virus; chickens; complementary DNA; cytogenetics; enzyme mechanism; epidermal growth factor; growth factor receptors; hematopoietic growth factor; leukemia; molecular cloning; mutagens; neoplasm /cancer genetics; oncogenes; protein kinase; protooncogene

A number of the cellular genes which upon mutation are capable of inducing cellular transformation (proto-oncogenes) have recently been identified as components involved in the normal cellular growth pathways. Recently, the oncogene responsible for avian erythroblastosis, erb B, has been shown to represent a truncated version of the epidermal growth factor receptor (EGF-R). This oncogene offers a unique opportunity to study the relationship between growth factor receptors and leukemia, and the process of oncogenic conversion of a normal cellular gene. It has been demonstrated that the c-erb B gene is mutated consistently in leukemia induced by a non-acute retrovirus. The mutation by viral DNA insertion is very specific and reproducible results in the production of a truncated c-erb B/EGF-R gene product that contains only the protein kinase domain. Presumably, this process constitutively activates the EGF-R receptor function leading to the uncontrolled growth of the target cell. In an effort to better understand the molecular basis for this process, the c-DNA clones corresponding to the activated c-erb B/EGF-R gene have been isolated from leukemic cells. Using these clones, we have constructed an avian leukemia model by inserting an activated c- erb B gene into a competent retroviral vector. The Rous/erb B virus (REB) is leukemogenic in chickens and appears to have tissue specificity. In this study we plan to: 1) Further characterize the REB virus and define the oncogenic determinants of its c-erb B gene product using site specific in vitro mutagenesis techniques; 2) Characterize the biochemical properties of the c-erb B gene product in its activated form and in its proto-oncogene form; 3) Determine the effect of activated c-erb B expression on the abrogation of growth factor dependence of hematopoietic cells.

一些细胞基因在突变时能够