Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent with its role in myelodysplastic syndromes
| Autor: | Hubert Hackl, Rotraud Wieser, Irene Herbacek, Anna Karger, Torsten A. Konrad, Ilse Schwarzinger |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Myeloid
Cellular differentiation Immunology DNA Fragmentation Phosphatidylserines Biology Cell Development Differentiation & Trafficking Resting Phase Cell Cycle hemic and lymphatic diseases Proto-Oncogenes medicine Immunology and Allergy Humans Myeloid Cells U937 cell Cell growth apoptosis G1 Phase Cell Differentiation Cell Biology U937 Cells Cell cycle medicine.disease ecotropic viral integration site 1 MDS1 and EVI1 Complex Locus Protein Cell biology DNA-Binding Proteins Leukemia Leukemia Myeloid Acute medicine.anatomical_structure cell proliferation Apoptosis Cell culture Myelodysplastic Syndromes Transcription Factors |
| Zdroj: | Journal of Leukocyte Biology |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | EVI1, a gene involved in myelodysplastic syndromes, causes growth arrest and cell death in U937 cells. The oncogene EVI1 has been implicated in the etiology of AML and MDS. Although AML cells are characterized by accelerated proliferation and differentiation arrest, MDS cells hyperproliferate when immature but fail to differentiate later and die instead. In agreement with its roles in AML and in immature MDS cells, EVI1 was found to stimulate cell proliferation and inhibit differentiation in several experimental systems. In contrast, the variant protein MDS1/EVI1 caused the opposite effect in some of these assays. In the present study, we expressed EVI1 and MDS1/EVI1 in a tetracycline-regulable manner in the human myeloid cell line U937. Induction of either of these proteins caused cells to accumulate in the G0/G1-phase of the cell cycle and moderately increased the rate of spontaneous apoptosis. However, when EVI1- or MDS1/EVI1-expressing cells were induced to differentiate, they massively succumbed to apoptosis, as reflected by the accumulation of phosphatidylserine in the outer leaflet of the plasma membrane and increased rates of DNA fragmentation. In summary, these data show that inducible expression of EVI1 in U937 cells causes phenotypes that may be relevant for its role in MDS and provides a basis for further investigation of its contribution to this fatal disease. |
| Databáze: | OpenAIRE |
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