STUDIES OF THE V-<I>ETS</I> ETS1 AND FLI1 TRANSCRIPTION FACTORS IN HEMATOPOIETIC

造血中V-<I>ETS</I> ETS1和FLI1转录因子的研究

• 批准号: 6289123
• 负责人: DONALD BLAIR
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289123
• 关键词: CD antigens; Retroviridae; athymic mouse; cell differentiation; cell growth regulation; cell transformation; cytosine arabinoside; gene expression; gene induction /repression; genetic markers; hematopoiesis; hematopoietic stem cells; heme; megakaryocytes; nucleic acid sequence; oncogenes; oncogenic virus; tissue /cell culture; transcription factor

The ETS family of transcription factors have been shown to be associated cell proliferation and a variety on neoplastic transforming events, especially those involving the erythroid lineage. We have been interested in the role of the ETS-1 and FLI-1 genes, two members of the ETS family of transcription factors, in hematopoeitic neoplasia and normal differentiation. Members of the ETS family have been shown to be involved in aspects of both erythroid and megakaryocytic differentiation in vivo. Our previous work had indicated that FLI-1 acted positively in certain pluripotent human hematopoeitic cell lines to activate genes normally expressed during megakaryocytic differentiaton, while blocking expression of genes associated with erythroid differentiation. We have extended our studies of the mechanisms by which MKK/MAPK and FLI-1 both can activate the expression of megakaryocytic markers in K562 and HEL cells. Our data indicate that these effects may involve two separate pathways, and that the presence of exogenous FLI-1 alters the effects of MKK/MAPK activation and inhibition. In addition these studies suggest that the regulation of the gpII_B and gpIII_A protein levels may be differentially affected by these pathways. - erythroid, ETS1, FLI1, HEL, hematopoiesis, K, 2, megakaryocyte, transcription factor, - Neither Human Subjects nor Human Tissues

ETS转录因子家族被证明与细胞增殖和多种肿瘤转化事件有关，特别是那些涉及红系的转录因子。我们对Ets转录因子家族中的两个成员Ets-1和Fli-1基因在造血肿瘤和正常分化中的作用一直很感兴趣。ETS家族成员已被证明参与体内红系和巨核细胞分化的各个方面。我们以前的工作表明，在某些多能人类造血细胞系中，Fli-1正向激活巨核细胞分化过程中正常表达的基因，同时抑制与红系分化相关的基因的表达。我们扩大了对MKK/MAPK和Fli-1在K562和HEL细胞中激活巨核细胞标志物表达的机制的研究。我们的数据表明，这些效应可能涉及两条不同的途径，外源Fli-1的存在改变了MKK/MAPK的激活和抑制效应。此外，这些研究表明，gpII_B和gpIII_A蛋白水平的调节可能受这些途径的不同影响。-红系，ETS1，FLI1，HEL，造血，K，2，巨核细胞，转录因子-既不是人也不是人的组织