Increased expression of the ETS-related transcription factor FLI-1/ERGB correlates with and can induce the megakaryocytic phenotype.
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.
Athanasiou
M
M
SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Clausen
P A
PA
Mavrothalassitis
G J
GJ
Zhang
X K
XK
Watson
D K
DK
Blair
D G
DG
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D039421:Integrin alpha2; D004915:Leukemia, Erythroblastic, Acute; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D016192:Resting Phase, Cell Cycle; D012190:Retroviridae / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C078433:FLI1 protein, human; C497426:Fli1 protein, mouse; D006454:Hemoglobins; D039421:Integrin alpha2; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D013755:Tetradecanoylphorbol Acetate