FUNCTIONAL ROLE OF FLI-1 IN NEOPLASIA

小鼠红白血病的特征表明， 至少三个ets家族成员（v-ets、Fli-1和Spi-1）。 过去几年 我们已经鉴定和表征了ETS癌基因家族的许多成员。 小鼠Fli-1基因在75%的红白血病中重排 由Friend鼠白血病病毒诱导。 最近我们克隆了 人类Fli-1基因。 这些cDNA克隆的分析 揭示了该基因与另一个ets家族成员高度同源， erg，我们之前已经确认了。 我们建议宽银幕 各种人类实体瘤和白血病的可能重排 Fli-1基因。 我们打算比较正常和异常的Fli-1基因座， 了解人Fli-1基因的激活机制。 以前我们已经证明，erg基因是高度同源的Fli- 1基因，编码序列特异性DNA结合蛋白，也作为 转录激活因子。 因此我们计划表达人类Fli-1 基因在细菌和哺乳动物细胞中，识别和表征 proteins. 我们打算研究正常人和 Fli-1基因异常。 我们还建议研究DNA结合， Fli-1基因产物的转录激活特性及其研究 它们在Fli-1基因的致癌特性中的作用。 我们计划研究 Fli-1与其他核癌基因的协同作用，并研究其 影响其生物化学和生物学特性。 我们打算 研究蛋白质-蛋白质相互作用对正常和异常Fli的作用， 1例蛋白质沉积。

Characterization of mouse erythroleukemias suggested involvement of at least three ets family members (v-ets, Fli-1 and Spi-1). Last few years we have identified and characterized many members of ets oncogene family. Mouse Fli-1 gene is shown to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. Recently we have cloned and characterized the human Fli-1 gene. Analysis of these cDNA clones revealed that this gene is highly homologous to another ets family member erg, which was previously identified by us. We propose to screen wide variety of human solid tumors and leukemias for possible rearrangements of Fli-1 gene. We intend to compare the normal and aberrant Fli-1 locus to understand the mechanism of activation of human Fli-1 gene. Previously we have shown that erg gene which is highly homologous to Fli- 1 gene, codes for sequence specific DNA binding proteins and also act as transcriptional activators. Therefore we plan to express human Fli-1 gene in bacteria and mammalian cells, identify and characterize the proteins. We intend to study the oncogenic potential of normal and aberrant Fli-1 gene. We also propose to study DNA binding and transcriptional activation properties of Fli-1 gene products and study their role in oncogenic properties of Fli-1 gene. We plan to study the cooperativity of Fli-1 with other nuclear oncogenes and study their effect on their biochemical and biological properties. We intend to study the role of protein-protein interaction on normal and aberrant Fli- 1 proteinsinneoplasia.