The Runx1 transcription factor controls CSF-1-dependent and -independent growth and survival of macrophages
| Autor: | Christine Mulford, Stephen L. Cronau, David A. Hume, Stewart R. Himes |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Cell Survival Molecular Sequence Data Receptor Macrophage Colony-Stimulating Factor Biology Mice chemistry.chemical_compound Proto-Oncogene Proteins hemic and lymphatic diseases Gene expression Genetics Animals Humans Progenitor cell Promoter Regions Genetic Molecular Biology Transcription factor Cell Proliferation Regulation of gene expression Base Sequence Cell growth Macrophage Colony-Stimulating Factor Macrophages Myeloid leukemia Cell biology DNA-Binding Proteins Mice Inbred C57BL Gene Expression Regulation RUNX1 chemistry Leukemia Myeloid Core Binding Factor Alpha 2 Subunit embryonic structures Cancer research Ectopic expression Transcription Factors |
| Zdroj: | Oncogene. 24:5278-5286 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1208657 |
| Popis: | Gene translocations that repress the function of the Runx1 transcription factor play a critical role in the development of myeloid leukemia. In this report, we demonstrate that Runx1 precisely regulates c-fms (CSF-1 receptor) gene expression. Runx1 controlled expression by binding to multiple sites within the mouse c-fms gene, allowing interaction between promoter and downstream enhancer elements. The runx1 and c-fms genes showed an identical pattern of expression in mature macrophages. Runx1 expression was repressed in CSF-1 stimulated, proliferating bone marrow-derived macrophages (BMM) and significantly increased in quiescent, CSF-1 starved cells. The RAW264.7 and Mono-Mac-6, macrophage-like cell lines expressed low levels of Runx1 and both showed growth arrest and cell death with ectopic expression of Runx1. The EM-3 cell line, which represents an early myeloid progenitor cell line, showed growth arrest with Runx1 expression in the absence of any detectable changes in cell differentiation. These findings suggest that Runx1 regulates growth and survival of myeloid cells and provide a novel insight into the role of Runx family gene translocations in leukemogenesis. |
| Databáze: | OpenAIRE |
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