TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

LMO的一项主要努力是通过以下方式阐明这些过程 哪些特定的逆转录病毒癌基因以及它们的细胞 同系物，能够影响关键的细胞事件。vbl.使用 禽类逆转录病毒癌基因ets和myc，作为探针，我们有 检测、分离、克隆和测序该病毒的细胞同源物 这些基因来自进化上不同的生物，如人类， 老鼠、鱼、海胆、非洲爪哇和果蝇。有一个家庭 在这些原ETS基因中，这些细胞的特定区域 基因保持在非常高的同源性水平；每一个 将原ETS癌基因与其病毒同源基因进行比较。总而言之， 5例中，原癌基因的大小远远大于 相应的病毒致癌基因。的一致截断 病毒癌基因及其产物的改变牵涉到 这种类型的损害作为一般事件导致 破坏这些高度保守的基因的功能。我们 还开发了几个表达载体 原核生物和真核生物产生癌基因的系统- 具体产品在数量上。这些表达产物被用来 纯化、鉴定和开发免疫试剂以定位 并对细胞原癌基因产物进行表征。是这样的 试剂也被用来探测表达 癌基因特异性产物在正常和恶性组织中的表达 将它们与特定的人类病理联系起来。我们已经能够 ETS基因产物的分离、鉴定及鉴定 该基因的一些相关性质与其功能有关 在信号转导途径和T4细胞成熟过程中。它 这些原ETS基因似乎也可能起着重要的作用 在唐氏综合征(DS)中，可能与更高的 比DS患者白血病的正常发病率高。

A major effort by the LMO has been to elucidate the processes by which specific retroviral oncogenes, as well as their cellular homologs, are able to impact on critical cellular events. Using the avian retroviral oncogenes, ets and myc, as probes, we have detected, isolated, cloned and sequenced the cellular homologs of these genes from evolutionarily diverse organisms such as humans, mice, fish, sea urchin, Xenopus and Drosophila. There is a family of these proto-ets genes where specific regions of these cellular genes are retained at very high levels of homology; each of these proto-ets oncogenes was compared to their viral homologs. In all cases, the proto-oncogenes were much larger than their corresponding viral oncogenes. The consistent truncation of the viral oncogene and consequent alteration of its products implicates this type of damage as a general event that results in the disruption of the function of these highly conserved genes. We have also developed and exploited several expression vector systems, both prokaryotic and eukaryotic, to produce oncogene- specific products in quantity. These expressed products were used to purify, characterize and develop immunologic reagents to locate and characterize the cellular proto-oncogene products. Such reagents have also been used to probe for the expression of oncogene-specific products in normal and malignant tissues and related them to specific human pathologies. We have been able to isolate and characterize the gene products of ets and determine some relevant properties of this gene that implicate its function in the signal transduction pathway and in T4 cell maturation. It also seems that these proto-ets genes may play a significant role in Down's syndrome (DS), and may possibly be related to the higher than normal incidence of leukemic disease seen in DS patients.