FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells
FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells
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DOI：
10.1038/sj.leu.2401689
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发表时间：
2000-03-01
期刊：
影响因子：
11.4
通讯作者：
Blair, DG
中科院分区：
文献类型：
--
作者：
Athanasiou, M;Mavrothalassitis, G;Blair, DG
FLI-1癌基因是ETS转录因子家族的成员，与正常和异常造血细胞生长和谱系特异性分化相关。我们先前已经表明，FLI-1在多能造血细胞中的过表达导致巨核细胞表型的诱导。在这份报告中，我们表明，FLI-1也作为红系分化的抑制剂。在诱导红系分化后，多能细胞表达降低水平的FLI-1。相反，当FLI-1在这些细胞中过表达时，红系标志物的水平降低。FLI-1过表达细胞对红系特异性诱导剂如氯化血红素和Ara-C的应答能力也受到抑制，未诱导的细胞显示红系相关加塔-1转录因子mRNA水平降低。此外，通过与表达FLI-1的构建体共转染，加塔-1启动子驱动的报告基因构建体在K562细胞中的表达被抑制。我们的结果支持FLI-1在造血细胞分化的调节中既可以起正作用也可以起负作用的假设，并且加塔-1表达的抑制可能有助于FLI-1介导的红系分化抑制。
The FLI-1 oncogene, a member of the ETS family of transcription factors, is associated with both normal and abnormal hematopoietic cell growth and lineage-specific differentiation. We have previously shown that overexpression of FLI-1 in pluripotent human hematopoietic cells leads to the induction of a megakaryocytic phenotype. In this report we show that FLI-1 also acts as an inhibitor of erythroid differentiation. Following the induction of erythroid differentiation, pluripotent cells express reduced levels of FLI-1, In contrast, when FLI-1 is overexpressed in these cells, the levels of erythroid markers are reduced. The ability of FLI-1 overexpressing cells to respond to erythroid-specific inducers such as hemin and Ara-C is also inhibited, and the uninduced cells show a reduced level of the erythroid-associated GATA-1 transcription factor mRNA. Furthermore, expression of a GATA-1 promoter-driven reporter construct in K562 cells is inhibited by co-transfection with a construct expressing FLI-1, Our results support the hypothesis that FLI-1 can act both positively and negatively in the regulation of hematopoietic cell differentiation, and that inhibition of GATA-1 expression may contribute to FLI-1-mediated inhibition of erythroid differentiation.