A colony-stimulating factor 1 (CSF-1) receptor/platelet-derived growth factor-beta receptor gene fusion confers CSF-1 independence and tumorigenicity on a c-myc-immortalized monocyte cell line.
Monocytes and macrophages express the receptor for the hematopoietic growth factor colony-stimulating factor 1 (CSF-1) and require this factor for growth in culture. A murine monocyte tumor cell line that lacks the usual requirement for CSF-1 was isolated. On the basis of the similarity of the structures of the CSF-1 and platelet-derived growth factor (PDGF) receptors and because monocytes normally secrete PDGF, we analyzed the tumor cell line for anomalous expression of the PDGF-R beta gene. Two different cDNAs that each contain sequences corresponding to the complete coding sequence of PDGF-R beta fused (in frame) to the amino-terminal half of the CSF-1 receptor were isolated. Introduction of these PDGF-R beta-related cDNAs into two partially transformed, CSF-1-dependent monocyte cell lines resulted in autonomous growth and cell transformation. These monocyte cell lines exhibit a novel form of growth factor receptor activation that can lead to oncogenic growth in collaboration with the c-myc oncogene.
Eccles
M R
MR
Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
King
F J
FJ
Cole
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA; D016259:Genes, myc; D005822:Genetic Vectors; D007739:L Cells; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015183:Restriction Mapping; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D016186:Receptor, Macrophage Colony-Stimulating Factor; D017479:Receptors, Platelet-Derived Growth Factor