Athanasiou M, Clausen P A, Mavrothalassitis G J, Zhang X K, Watson D K, Blair D G
SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Cell Growth Differ. 1996 Nov;7(11):1525-34.
The human leukemia cell line K562 can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the megakaryocytic pathway, generating morphological changes and increased expression of lineage-specific surface markers. We report that TPA-treated K562 cells also express higher levels of FLI-1/ERGB, a member of the ETS family of transcription factors. Furthermore, introduction of a retroviral construct expressing human FLI-1/ERGB into K562 cells induces changes similar to those seen following TPA treatment, including increased adherence to the surface of the culture vessel and altered size and morphology. Infected cells exhibit higher levels of the megakaryocyte marker CD41a and, to a lesser extent, CD49b. These markers, as well as virally encoded FLI-1/ERGB-specific RNA and protein, are expressed at the highest levels in the attached cell population, while the growth rate of adherent cells is reduced, and the fraction of cells in G0-G1 is increased. FLI-1/ERGB virus-infected cells also exhibit increased expression of hemoglobin, a marker of erythroid differentiation. Our results suggest FLI-1/ERGB plays a role in controlling differentiation and gene expression along the megakaryocyte/platelet pathway, and further implicate ETS-related genes in the control of multiple developmentally regulated hematopoietic genes.
人白血病细胞系K562可被十四酰佛波醇乙酯（TPA）诱导沿巨核细胞途径分化，产生形态变化并增加谱系特异性表面标志物的表达。我们报道，经TPA处理的K562细胞还表达更高水平的FLI-1/ERGB，它是ETS转录因子家族的成员。此外，将表达人FLI-1/ERGB的逆转录病毒构建体导入K562细胞可诱导出与TPA处理后相似的变化，包括增加对培养容器表面的黏附以及改变大小和形态。被感染的细胞表现出更高水平的巨核细胞标志物CD41a，以及较低水平的CD49b。这些标志物以及病毒编码的FLI-1/ERGB特异性RNA和蛋白质在贴壁细胞群体中表达水平最高，而贴壁细胞的生长速率降低，处于G0-G1期的细胞比例增加。FLI-1/ERGB病毒感染的细胞还表现出血红蛋白表达增加，这是红系分化的标志物。我们的结果表明FLI-1/ERGB在控制巨核细胞/血小板途径的分化和基因表达中发挥作用，并进一步表明ETS相关基因参与控制多个发育调控的造血基因。
