INTERACTIONS OF V-ERBA/V-ERBB/ BAND 3 IN ERYTHROLEUKEMIA

禽成红细胞增多症病毒（AEV）携带两种癌基因，v-erbA和v-erbB。 b. 这两个基因在引起禽红白血病中的协同作用 提供了一个多步骤致癌的模型系统。 而v-erbB是 需要和足以引起转变，转变只是 在也携带v-erbA基因的细胞中稳定。 细胞的表型 仅携带一种癌基因的肿瘤细胞表明v-erbA 而v-erbB在引起红白血病中是通过抑制 带3基因。 这些细胞的特征进一步表明 带3蛋白可以作为v-erbB转化的拮抗剂， 功能 我们认为，v-erbB酪氨酸激酶不能稳定表达， 因为不能完全抑制 带3基因表达。 我们进一步认为，v-erbA转录 因子通过抑制带3的转录来稳定转化 基因 本建议探讨第3类在发展禽流感方面的作用。 红白血病 我们将直接测试带3诱导 通过人工调节V-erbB转化细胞的分化， 胞内带3浓度。 第三等级将增加 使用逆转录病毒载体表达外源带3 cDNA， 瞬时实验和通过使用诱导型启动子调节 在稳定转染子中表达。 内源性带3表达将 通过表达反义带3 RNA减少或消除。 的作用 v-erbA在带3转录调节中的作用将由以下定义： 带3基因中相互作用的调节序列的鉴定 与v-erbA直接或响应于v-erbA控制的 调节级联。

The avian erythroblastosis virus (AEV) carries two oncogenes, v-erbA and v- erbB. The cooperation of these two genes in causing avian erythroleukemias provides a model system for multistep carcinogenesis. While v-erbB is required and sufficient to cause transformation, transformation is only stabilized in cells which also carry a v-erbA gene. The phenotype of cells which carry only one oncogene suggests that the synergism between v-erbA and v-erbB in causing erythroleukemias is mediated through the suppression of the band 3 gene. The characteristics of these cells further suggests that the band 3 protein can act as an antagonist to the v-erbB transforming function. We suggest that the v-erbB tyrosine kinase is unable to stably transform avian erythroblasts because of an inability to completely repress band 3 gene expression. We further suggest that the v-erbA transcription factor stabilizes transformation by suppression transcription of the band 3 gene. This proposal examines the role of band 3 in the development of avian erythroleukemias. We will directly test the ability of band 3 to induce differentiation in v-erbB transformed cells by artificially regulating the intracellular band 3 concentrations. Band 3 levels will be increased by the expression of an exogenous band 3 cDNA using retroviral vectors for transient experiments and by using an inducible promoter to regulate expression in stable transfectants. The endogenous band 3 expression will be reduced or eliminated by expression antisense band 3 RNA. The role of v-erbA in the regulation of band 3 transcription will be defined by the identification of regulatory sequences in the band 3 gene which interact with v-erbA directly or which function in response to a v-erbA-controlled regulatory cascade.