Leukemogenesis by Murine Retroviruses

描述（由申请方提供）：小鼠白血病病毒（MuLV）是一种强效病毒， 小鼠造血肿瘤的诱导物。转录调节序列 在这些病毒的长末端重复序列（LTR）内控制表达 在肿瘤发生过程中起着至关重要的作用， 这些病毒。他们确定特定MuLV引起的肿瘤类型， 影响病毒感染致病靶细胞的能力， 它们在细胞基因的致瘤激活中发挥作用， 病毒基因组的相邻插入。这里提出的实验， 比较不同MuLV在模板上的转录能力， 整合在小鼠基因组的不同位点。这些实验将使用 这些病毒引起肿瘤的细胞谱系。的第二线 实验提出，以确定细胞基因被激活， 并开始测试这些基因是如何参与 肿瘤发生高通量技术现在是可用的，其允许这样的 基因筛查的速度将比过去快得多。这 方法将应用于两个单独的MuLV肿瘤系统。那些基因 在这些屏幕中确定的，预计将提供有关重要和 也许是意想不到的分子机制，有助于产生 白血病和淋巴瘤。

DESCRIPTION (provided by applicant): Murine leukemia viruses (MuLVs) are potent inducers of hematopoietic tumors in mice. Transcriptional regulatory sequences within the long terminal repeats (LTRs) of these viruses control the expression of the viral genomes and play crucial roles in the process of tumorigenesis by these viruses. They determine the type of tumor that specific MuLVs cause, they influence the ability of the viruses to infect the target cells for disease, and they play a role in the tumorigenic activation of cellular genes following adjacent insertion of the viral genomes. Experiments are proposed here to compare the transcriptional capacity of different MuLVs on templates that are integrated at various sites in the mouse genome. These experiments will use cells from the lineages in which these viruses cause tumors. A second line of experiments is proposed to identify the cellular genes that are activated by these viruses in tumors and to begin to test how these genes participate in tumorigenesis. High-throughput technology is now available that allows such genetic screens to be performed far more rapidly than in the past. This approach will be applied to two separate MuLV tumor systems. The genes that are identified in these screens are expected to provide insight about important and perhaps unanticipated molecular mechanisms that contribute to the generation of leukemias and lymphomas.