Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P07332 (feline sarcoma)
 360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-fms gene encodes the receptor for the macrophage colony-stimulating factor, which plays a key role in the proliferation and differentiation of cells of the myelomonocytic lineage. In order to study the effects of overexpression of the macrophage colony-stimulating factor receptor in hematopoietic cells, a Harvey sarcoma virus-derived retroviral vector containing the murine c-fms cDNA was pseudotyped with Friend murine leukemia virus and inoculated into newborn DBA/2 mice. This viral complex induced monoclonal or oligoclonal leukemias with a shorter latency than that for Friend murine leukemia virus alone. Unexpectedly, 60% of the integrated fms proviruses had deletions at the 5' end of the c-fms gene. Sequence analysis of seven mutant proviruses indicated that the deletions always included the c-fms ligand binding domain and either occurred within the c-fms sequences, leaving the fms open reading frame unchanged, or joined VL30 sequences located at the 5' end of the parental retroviral vector to internal c-fms sequences, resulting in truncated fms proteins devoid of the canonical signal peptide. In contrast to all tyrosine kinase receptors transduced in retroviruses, no helper gag- or env-derived sequences were fused to the rearranged fms sequences. Viral supernatants isolated from hematopoietic tumors with viruses with deletions were able to transform NIH 3T3 cells as efficiently as parental fms virus, indicating that deletions resulted in constitutive activation of the c-fms gene. These oncogenic variants differ from those transduced in the Suzan McDonough strain of feline sarcoma viruses (L. Donner, L. A. Fedele, C. F. Garon, S. J. Anderson, and C. J. Sherr, J. Virol. 41:489-500, 1982). The high rate of c-fms rearrangement and its relevance in the occurrence of hematopoietic tumors are discussed.
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PMID:Isolation of new oncogenic forms of the murine c-fms gene. 774 7

We examined six human short tandem repeat (STR) loci (c-fms proto-oncogene for CSF-1 receptor, CSF1PO; thyroid peroxidase, TPOX; tyrosine hydroxylase, TH01; coagulation factor XIII a subunit, F13A01; c-fes/fps proto-oncogene, FESFPS and von Willebrand factor, vWA) in the Japanese macaque, Macaca fuscata, using commercially available human STR kits. No products were amplified by polymerase chain reaction (PCR) using the human CSF1PO, TH01, FESFPS and vWA primers. Macaque DNAs were amplified with human TPOX and F13A01 primers. Macaque PCR products amplified with the TPOX and F13A01 primers migrated more slowly than human ones during electrophoresis. Sequencing results showed that the nucleotide sequences of the counterpart of the TPOX and F13A01 STR loci in the Japanese macaque were closely similar to those of the human genes except for tandem repeat regions. The macaque products amplified with human TPOX and F13A01 primers were highly polymorphic, with four variants of the former and 15 variants of the latter in the nine samples. These results indicate that the commercially available kits can be used to discriminate the Japanese macaque samples from human samples.
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PMID:Evaluation of the species specificity for six human short tandem repeat loci CSF1PO, TPOX, TH01, F13A01, FESFPS and vWA, in the Japanese macaque. 1503 53

The cFMS (cellular homolog of the V-FMS oncogene product of the Susan McDonough strain of feline sarcoma virus) (Proc Natl Acad Sci U S A 83:3331-3335, 1986) kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) inhibits colony-stimulating factor (CSF)-1-induced monocyte growth and bone degradation in vitro and inhibits CSF-1 signaling through cFMS kinase in 4-day models in mice (Proc Natl Acad Sci U S A 102:16078, 2005). In the present study, the kinase selectivity of GW2580 was further characterized, and the effects of chronic treatment were evaluated in normal and arthritic rats. GW2580 selectively inhibited cFMS kinase compared with 186 other kinases in vitro and completely inhibited CSF-1-induced growth of rat monocytes, with an IC(50) value of 0.2 microM. GW2580 dosed orally at 25 and 75 mg/kg 1 and 5 h before the injection of lipopolysaccharide inhibited tumor necrosis factor-alpha production by 60 to 85%, indicating a duration of action of at least 5 h. In a 21-day adjuvant arthritis model, GW2580 dosed twice a day (b.i.d.) from days 0 to 21, 7 to 21, or 14 to 21 inhibited joint connective tissue and bone destruction as assessed by radiology, histology and bone mineral content measurements. In contrast, GW2580 did not affect ankle swelling in the adjuvant model nor did it affect ankle swelling in a model where local arthritis is reactivated by peptidoglycan polysaccharide polymers. GW2580 administered to normal rats for 21 days showed no effects on tissue histology and only modest changes in serum clinical chemistry and blood hematology. In conclusion, GW2580 was effective in preserving joint integrity in the adjuvant arthritis model while showing minimal effects in normal rats.
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PMID:Effects of the cFMS kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) in normal and arthritic rats. 1843 89


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