Transcriptional regulation of the c-fms proto-oncogene mediated by granulocyte/macrophage colony-stimulating factor (GM-CSF) in murine cell lines.
Differentiation of blood cells is paralleled by a timely ordered expression of cytokine receptor genes. We show here that the expression of the c-fms gene which encodes the lineage-specific receptor for macrophage colony-stimulating factor (M-CSF or CSF-1) is directly linked to ligand-mediated activation of the receptor for the granulocyte/macrophage colony-stimulating factor (GM-CSF). In interleukin-3 (IL-3) dependent multipotent progenitor cells, FDC-Pmix GMV#2 cells, GM-CSF treatment results in the rapid formation of full-length c-fms transcripts. Surprisingly, this upregulation of c-fms transcripts is also observed in mouse NIH3T3 fibroblasts stably transfected with genes coding for the alpha- and beta-subunits of the GM-CSF receptor. These results indicate a direct control by the GM-CSF receptor that takes place regardless of cell differentiation. Furthermore, a 2.1 kb genomic fragment containing the c-fms proximal promoter directs GM-CSF-inducible expression of a reporter gene, suggesting a regulation of c-fms gene expression on the transcriptional level.
Helftenbein
G
G
Institut für Virologie, Justus-Liebig Universität Giessen, Germany.
Krusekopf
K
K
Just
U
U
Cross
M
M
Ostertag
W
W
Niemann
H
H
Tamura
T
T
D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D016236:Genes, fms; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000166:cytology; D051379:Mice; D011401:Promoter Regions, Genetic; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D007377:Interleukin-3; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor