FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells

• Published in: Leukemia Vol. 14; no. 3; pp. 439 - 445
• Main Authors: ATHANASIOU, M, MAVROTHALASSITIS, G, SUN-HOFFMAN, L, BLAIR, D. G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.03.2000; Nature Publishing Group
• Subjects: Biological and medical sciences; Cell differentiation; Cell Differentiation - drug effects; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cytarabine - pharmacology; Differentiation (biology); DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Erythrocytes - cytology; Erythroid Precursor Cells - cytology; Erythroid Precursor Cells - drug effects; Erythroid Precursor Cells - metabolism; Erythroid-Specific DNA-Binding Factors; Erythropoiesis - drug effects; Erythropoiesis - physiology; ETS protein; FLI-1 protein; Fundamental and applied biological sciences. Psychology; GATA1 Transcription Factor; Gene expression; Gene Expression Regulation, Leukemic - drug effects; Hemin; Hemin - pharmacology; Humans; K562 Cells - cytology; K562 Cells - drug effects; K562 Cells - metabolism; Megakaryocytes - cytology; Molecular and cellular biology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phenotypes; Pluripotency; Promoter Regions, Genetic; Proto-Oncogene Protein c-fli-1; Proto-Oncogene Proteins; Recombinant Fusion Proteins - physiology; RNA, Messenger - biosynthesis; RNA, Neoplasm - biosynthesis; Trans-Activators - biosynthesis; Trans-Activators - genetics; Trans-Activators - physiology; Transcription factors; Transcription Factors - metabolism; Transfection; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism; Human; Regulation(control); Erythroid cell; Transcription promoter; C-Onc gene; Established cell line; Hematopoietic cell; Cell differentiation; Protooncogene; Transcription factor GATA1
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2401689

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.