A COLONY-STIMULATING FACTOR-I (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 from of growth factor activation that can lead to oncogenic growth in collaboration with the c-myc oncogene.