FUNCTIONAL ROLE OF FLI-1 IN NEOPLASIA

小鼠红白血病的特征提示AT参与 至少三个ETS家族成员(v-ETS、Fli-1和SPi-1)。过去几年 我们已经鉴定并鉴定了许多ETS癌基因家族的成员。 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 确定了人类Fli-1基因的特征。这些cDNA克隆的序列分析 显示该基因与ETS家族的另一成员高度同源 ERG，这是我们之前确认的。我们建议放映大屏幕 人类实体瘤和白血病的各种可能的重排 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基因激活的机制。 以前我们已经证明了erg基因与fli-1高度同源。 1基因，编码序列特异的DNA结合蛋白，也起到 转录激活剂。因此，我们计划表达人Fli-1 细菌和哺乳动物细胞中的基因，鉴定和表征 蛋白质。我们打算研究正常人和正常人的致癌潜能。 Fli-1基因异常。我们还建议研究DNA结合和 Fli-1基因产物的转录激活特性及其研究 它们在Fli-1基因致癌特性中的作用。我们计划研究 Fli-1与其他核癌基因的协同作用及其机制研究 对其生化和生物学特性的影响。我们打算 蛋白质-蛋白质相互作用在正常和异常血小板中的作用 蛋白质瘤变1例。

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.