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

V-ERBA/V-ERBB/带 3 在红白血病中的相互作用

• 批准号: 3196649
• 负责人: LOUISE C. SHOWE
• 金额: $ 21.52万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-14 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3196649
• 关键词: Retroviridae; alpharetrovirus; antisense nucleic acid; avian lymphomatosis; chickens; complementary DNA; erythroleukemia; gene expression; genetic library; genetic promoter element; genetic transcription; intracellular; metallothionein; nucleic acid probes; nucleic acid sequence; oncogenes; oncogenic virus; protein structure; tissue /cell culture; transcription factor; transfection; viral carcinogenesis; virus RNA; virus virus interaction

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.

禽红母细胞病病毒（AEV）携带两种致癌基因，v- erba和v-