The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line.
The McDonough strain of feline sarcoma virus (SM-FeSV) transforms fibroblast cell lines in culture and produces fibrosarcomas in domestic cats. 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. The v-fms-coded polypeptide includes the complete extracellular domain of the c-fms proto-oncogene product and retains the ability to bind CSF-1 specifically. 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 product. Autophosphorylation of the c-fms gene product on tyrosine is enhanced by CSF-1 addition, whereas phosphorylation of the v-fms-coded glycoprotein appears to be constitutive. 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.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005814:Genes, Viral; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D005253:Sarcoma Viruses, Feline / Q000235:genetics*
D011505:Protein-Tyrosine Kinases