Colony stimulating factor-1 induced growth stimulation of v-fms transformed fibroblasts.
The v-fms oncogene, which is capable of transforming fibroblasts, was derived by recombination of a feline leukemia virus with a cellular gene (c-fms) that encodes the receptor for colony stimulating factor 1 (CSF-1). We examined the capacity of recombinant human CSF-1 (produced in a yeast expression system) to stimulate the growth of v-fms transformed rat fibroblasts. Recombinant human CSF-1 bound to v-fms transformed fibroblasts with high affinity (apparent Kd = 6.0 x 10(-10) M); only non-specific binding was observed on control cells. The number of colonies formed in soft agar by v-fms transformed cells was increased by CSF-1 treatment in a dose-dependent manner; a nine fold increase in the number of colonies was seen in the presence of 10(-8) M CSF-1. CSF-1 did not stimulate the growth of either non-transformed cell lines, a non-transformed cell line that expresses a mutated v-fms protein on the cell surface, or cells transformed by the v-fgr oncogene. The growth stimulating effect of CSF-1 on v-fms transformed cells was also seen in monolayer culture. The v-fms transformed cells treated with CSF-1 had a more refractile, rounded morphology than non-treated cells; no morphology change was observed in CSF-1 treated control cells. CSF-1 treatment also increased both the number and size of foci that arose from fibroblasts following transfection with the v-fms oncogene. These data show that the altered CSF-1 receptor encoded by the v-fms oncogene retains a capacity to bind, and be stimulated by, human CSF-1.
Lyman
S D
SD
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Park
L
L
Rohrschneider
L R
LR
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D005256:Leukemia Virus, Feline / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor; D016281:Oncogene Protein gp140(v-fms); D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014162:Transfection
D003115:Colony-Stimulating Factors; D016281:Oncogene Protein gp140(v-fms); D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor