Abstract
The McDonough strain of feline sarcoma virus (SM-FeSV) transforms fibroblast cell lines in culture and produces fibrosarcomas in domestic cats1,2. SM-FeSV does not induce haematopoietic malignancies in spite of the fact that its viral oncogene, v-fms, codes for a glycoprotein related to the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1 (refs 3, 4). The v-fms-coded polypeptide includes the complete extracellular domain of the c-fms proto-oncogene product5,6 and retains the ability to bind CSF-1 specifically4. The two molecules have very similar sequences except at their extreme carboxyl terminal ends where 40 amino acids of the c-fms-coded glycoprotein are replaced by 11 unrelated residues in the v-fms product5. Autophosphorylation of the c-fms gene product on tyrosine is enhanced by CSF-1 addition3, whereas phosphorylation of the v-fms-coded glycoprotein appears to be constitutive4. We now show that introduction of the v-fms gene into simian virus-40 (SV40)-immortalized, CSF-1 dependent macrophages renders them independent of CSF-1 for growth and tumourigenic in nude mice. These factor-independent cell lines express unaltered levels of the c-fms product which is down-modulated in response to either CSF-1 or the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The induction of factor independence by a non-autocrine mechanism suggests that the v-fms product is an unregulated kinase that provides growth stimulatory signals in the absence of ligand.
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Wheeler, E., Rettenmier, C., Look, A. et al. The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line. Nature 324, 377–380 (1986). https://doi.org/10.1038/324377a0
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DOI: https://doi.org/10.1038/324377a0
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