ANALYSIS OF THE CELLULAR ONCOGENE PROTO-MYB

细胞癌基因原-MYB 的分析

• 批准号: 3170069
• 负责人: DIANA K SHEINESS
• 金额: $ 10.83万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1988-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170069
• 关键词: T lymphocyte; alpharetrovirus; cell type; developmental genetics; evolution; gene expression; genetic library; genetic manipulation; genetic mapping; genetic regulation; genetic transcription; genome; immunochemistry; messenger RNA; methylation; molecular cloning; nucleic acid sequence; oncogenes; oncogenic virus; radiotracer; regulatory gene; synchronous cell division; tissue /cell culture

A host origin for retroviral oncogenes is implied by the discovery that vertebrate DNA contains highly conserved genes ("proto-oncogenes") that are homologous to retroviral oncogenes. The similarity between viral oncogenes and proto-oncogenes implies a normal role for proto-oncogenes in cell growth and/or differentiation. Our long-term goal is to elucidate the presumptive roles of proto-oncogenes as cancer genes and as regulators of normal cell growth. To that effect, we have conducted studies focused primarily on the expression of proto-myb, a proto-oncogene that corresponds to the transforming gene of the avian myeloblastosis virus. In current studies with mice, we have shown that proto-myb expression is confined exclusively to cells in early stages of differentiation in the hemopoietic lineages and that the highest level of proto-myb mRNA observed was that seen in the thymus. In other experiments, we have ruled out any correlation between expression of several proto-oncogenes and thymic involution. Preliminary results with cultured cells suggest furthermore that proto-myh mRNA levels are not dependent on the proliferative state of the cells. At present, our efforts are directed primarily towards cloning and characterizing the mouse proto-myb gene. By screening a library of mouse DNA in phage lambda, we have obtained clones of genome DNA that evidently contain the 5' end of the proto-myb gene. We have also isolated a cDNA clone containing 2.5 kb of sequence, most of which extends 3' of the cloned genome DNA. By restriction mapping, we have estimated a size of 40 Kb for the mouse proto-myb gene. Selected portions of the cloned DNAs are currently being sequenced. Additional efforts are underway to clone the remainder of the proto-myb gene and to study proto-myb expression thymocytes exposed to mitogens and hormones. (P)

这一发现暗示了逆转录病毒癌基因的宿主起源