Mouse NIH 3T3 cells expressing human colony-stimulating factor 1 (CSF-1) receptors overgrow in serum-free medium containing human CSF-1 as their only growth factor.
Mouse NIH 3T3 cells expressing the human c-fms protooncogene encoding the receptor for colony-stimulating factor 1 (CSF-1) are able to proliferate in serum-free medium containing platelet-derived growth factor (PDGF), insulin, transferrin, and albumin as the only exogenous proteins. When PDGF and insulin were replaced by purified human recombinant CSF-1, the cells became spindle shaped and refractile, were no longer contact inhibited, and proliferated to high densities. Thus, transduction of the human c-fms gene into mouse fibroblasts can not only reprogram their growth factor requirements but can also induce ligand-dependent features of cell transformation. NIH 3T3 cells stably transformed by the feline v-fms oncogene or by a mutated, oncogenic human c-fms gene were able to proliferate in the absence of exogenous growth factors. A monoclonal antibody that prevents signal transduction by the human CSF-1 receptor inhibited the growth of cells transformed by the activated c-fms oncogene, confirming that CSF-1 receptor function was required to abrogate growth factor requirements and to maintain the transformed state.
Roussel
M F
MF
Department of Tumor Cell Biology, Saint Jude Children's Research Hospital, Memphis, TN 38105.
Sherr
C J
CJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D015870:Gene Expression; D005796:Genes; D006801:Humans; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor; D051379:Mice; D008815:Mice, Inbred Strains; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface / Q000235:genetics*
D003115:Colony-Stimulating Factors; D003470:Culture Media; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor