Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genes, fms”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1982

McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms).

The genetic structure of the McDonough strain of feline sarcoma virus (SM-FeSV) was deduced by analysis of molecularly cloned, transforming proviral DNA. The 8.2-kilobase pair SM-FeSV provirus is longer than those of other feline sarcoma viruses and contains a transforming gene (v-fms) flanked by sequences derived from feline leukemia virus. The order of genes with respect to viral RNA is 5'-gag-fms-env-3', in which the entire feline leukemia virus env gene and an almost complete gag sequence are represented. Transfection of NIH/3T3 cells with cloned SM-FeSV proviral DNA induced foci of morphologically transformed cells which expressed SM-FeSV gene products and contained rescuable sarcoma viral genomes. Cells transformed by viral infection or after transfection with cloned proviral DNA expressed the polyprotein (P170gag-fms) characteristic of the SM-FeSV strain. Two proteolytic cleavage products (P120fms and pp55gag) were also found in immunoprecipitates from metabolically labeled, transformed cells. An additional polypeptide, detected at comparatively low levels in SM-FeSV transformants, was indistinguishable in size and antigenicity from the envelope precursor (gPr85env) of feline leukemia virus. The complexity of the v-fms gene (3.1 +/- 0.3 kilobase pairs) is approximately twofold greater than the viral oncogene sequences (v-fes) of Snyder-Theilen and Gardner-Arnstein FeSV. By heteroduplex, restriction enzyme, and nucleic acid hybridization analyses, v-fms and v-fes sequences showed no detectable homology to one another. Radiolabeled DNA fragments representing portions of the two viral oncogenes hybridized to different EcoRI and HindIII fragments of normal cat cellular DNA. Cellular sequences related to v-fms (designated c-fms) were much more complex than c-fes and were distributed segmentally over more than 40 kilobase pairs in cat DNA. Comparative structural studies of the molecularly cloned proviruses of Synder-Theilen, Gardner-Arnstein, and SM-FeSV showed that a region of the feline-leukemia virus genome derived from the pol-env junction is represented adjacent to v-onc sequences in each FeSV strain and may have provided sequences preferred for recombination with cellular genes.

Animals↗
PubMed1995

Induction of sustained expression of proto-oncogene c-fms by platelet-derived growth factor, epidermal growth factor, and basic fibroblast growth factor, and its suppression by interferon-gamma and macrophage colony-stimulating factor in human aortic medial smooth muscle cells.

Vascular medial smooth muscle cells migrate, proliferate and transform to foam cells in the process of atherosclerosis. We have reported that the intimal smooth muscle cells express proto-oncogene c-fms, a characteristic gene of monocyte-macrophages, which is not normally expressed in medial smooth muscle cells. In the present study, we demonstrated that combinations of platelet-derived growth factor (PDGF)-BB and either epidermal growth factor (EGF) or fibroblast growth factor (FGF) induced high expression of c-fms in normal human medial smooth muscle cells to the level of intimal smooth muscle cells or monocyte-derived macrophages, whereas c-fms expression by PDGF-BB alone was 1/10 and both EGF and FGF had no independent effect on c-fms expression. By contrast, interferon (IFN)-gamma and macrophage colony-stimulating factor (M-CSF) suppressed the induction of c-fms expression. These results indicate that multiple growth factors and cytokines may play a role in the phenotypic transformation of medial smooth muscle cells to intimal smooth muscle cells in atherosclerotic lesions by altering c-fms expression.

Aorta↗
PubMed1992

Cloning and structural analysis of the human c-kit gene.

The recent identification of the mouse White spotting and Steel loci as genes encoding the c-kit receptor and its ligand, respectively, has shed light on the importance of this ligand and receptor in embryogenesis, melanogenesis and hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in human disease, we isolated seven overlapping lambda recombinants, using a fetal brain cDNA, and characterized the normal human gene (KIT). The longest mapped transcript is 5230 bp, is alternatively spliced and includes 21 exons that span more than 70 kb of DNA. From the exon-intron structure, we have localized an alternative splice site to the 3' end of exon 9. The overall c-kit gene structure closely resembles that found in the CSF-1R gene (c-fms). This similarity includes a large first intron, the same number of exons containing translated sequence and very similar exon-intron boundaries. Using pulsed-field gel electrophoresis, we have linked KIT to the platelet-derived growth factor receptor A gene, with both residing on a 700-kb BssHI fragment. These data will allow investigation into the control of KIT expression and the potential to identify mutations or altered expression of this gene in human disease.

Base Sequence↗
PubMed1982

Monoclonal antibodies to the transformation-specific glycoprotein encoded by the feline retroviral oncogene v-fms.

Monoclonal antibodies prepared to epitopes encoded by the transforming gene (v-fms) of the McDonough strain of feline sarcoma virus were used to study v-fms-coded antigens in feline sarcoma virus-transformed rat and mink cells. These antibodies reacted with three different polypeptides (gP180gag-fms, gp140fms, and gp120fms), all of which were shown to be glycosylated. Protein blotting with [125I]-labeled monoclonal immunoglobulin G's was used to determine the relative steady-state levels of these glycoproteins in transformed cells and showed that gp120 and gp140 were the predominant products. Immunofluorescence assays and subcellular fractionation experiments localized these molecules to the cytoplasm of transformed cells in quantitative association with sedimentable organelles. Thus, v-fms-coded glycoproteins differ both chemically and topologically from the partially characterized products of other known oncogenes and presumably transform cells by a different mechanism.

Animals↗
PubMed1994

Possible involvement of VEGF-FLT tyrosine kinase receptor system in normal and tumor angiogenesis.

A novel receptor-type tyrosine kinase gene flt (fms-like tyrosine kinase, flt-1) was isolated from human placenta cDNA library. Flt-1 receptor carries a ligand binding domain which contains seven immunoglobulin-like stretches. Further, Flt-1 tyrosine kinase domain is separated by an approximately 70 amino acid-insert region similar to the cases of Fms/Kit/PDGF-R (fms family). However, unlike the fms family members, Flt-1 insert region does not contain "Tyr-X-X-Met" motif, which is known to be important for signal transduction and for the binding of P13 kinase to the receptor. Thus, a unique structure of Flt-1 suggests that a signal transduction pathway from Flt receptor is different from that in the fms family. The expression of flt-1 gene is detectable in a variety of normal tissues, and cell fractionation studies indicate that the flt-1 mRNA is highly expressed in endothelial cell-enriched fraction. VEGF, which has recently been reported as a ligand for Flt-1 receptor, dramatically stimulated growth of endothelial cells in culture. Many human tumors were found to express VEGF mRNA but not Flt-1 message, suggesting a paracrine mechanism for tumor angiogenesis. Interestingly, VEGF could not stimulate proliferation of Flt-1-overexpressing NIH3T3 fibroblast cells. These results suggest that Flt-1 is an endothel-specific growth factor receptor and that the signal transducing pathway through Flt-1 receptor is inactive in the fibroblast background.

3T3 Cells↗
PubMed1996

Transcriptional regulation of the c-fms proto-oncogene mediated by granulocyte/macrophage colony-stimulating factor (GM-CSF) in murine cell lines.

Differentiation of blood cells is paralleled by a timely ordered expression of cytokine receptor genes. We show here that the expression of the c-fms gene which encodes the lineage-specific receptor for macrophage colony-stimulating factor (M-CSF or CSF-1) is directly linked to ligand-mediated activation of the receptor for the granulocyte/macrophage colony-stimulating factor (GM-CSF). In interleukin-3 (IL-3) dependent multipotent progenitor cells, FDC-Pmix GMV#2 cells, GM-CSF treatment results in the rapid formation of full-length c-fms transcripts. Surprisingly, this upregulation of c-fms transcripts is also observed in mouse NIH3T3 fibroblasts stably transfected with genes coding for the alpha- and beta-subunits of the GM-CSF receptor. These results indicate a direct control by the GM-CSF receptor that takes place regardless of cell differentiation. Furthermore, a 2.1 kb genomic fragment containing the c-fms proximal promoter directs GM-CSF-inducible expression of a reporter gene, suggesting a regulation of c-fms gene expression on the transcriptional level.

3T3 Cells↗
PubMed1993

Expression of human colony-stimulating factor-1 (CSF-1) receptor in murine pluripotent hematopoietic NFS-60 cells induces long-term proliferation in response to CSF-1 without loss of erythroid differentiation potential.

NFS-60 and FDCP-Mix cells are interleukin-3--dependent multipotent hematopoietic cells that can differentiate in vitro into mature myeloid and erythroid cells. Retrovirus-mediated transfer of the human colony-stimulating factor-1 (CSF-1) receptor gene (c-fms) enabled NFS-60 cells but not FDCP-Mix cells to proliferate in response to CSF-1. The phenotype of NFS-60 cells expressing the human CSF-1 receptor (CSF-1R) grown in CSF-1 did not grossly differ from that of original NFS-60 as assessed by cytochemical and surface markers. Importantly, these cells retained their erythroid potentiality. In contrast, a CSF-1-dependent variant of NFS-60, strongly expressing murine CSF-1R, differentiated into monocyte/macrophages upon CSF-1 stimulation and almost totally lost its erythroid potentiality. We also observed that NFS-60 but not FDCP-Mix cells could grow in response to stem cell factor, (SCF), although both cell lines express relatively high amounts of SCF receptors. This suggests that SCF-R and CSF-1R signalling pathways share at least one component that may be missing or insufficiently expressed in FDCP-Mix cells. Taken together, these results suggest that human CSF-1R can use the SCF-R signalling pathway in murine multipotent cells and thereby favor self-renewal versus differentiation.

Animals↗
PubMed1991

A dominant suppressive mutation in a cellular gene restores the nontransformed phenotype to v-fms-transformed mink cells.

A nontransformed revertant subclone (GVR17) was isolated from mutagen-treated populations of mink epithelial cells which had been transformed by the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The revertant cells, although contact-inhibited for growth and unable to form colonies in semisolid medium, contained two copies of integrated SM-FeSV proviral DNA, expressed high levels of the v-fms oncogene product and its associated tyrosine kinase activity, and yielded rescuable viruses able to transform parental mink epithelial and mouse NIH3T3 cells. The transformed phenotype was suppressed in cell hybrids generated by fusing revertant and v-fms-transformed mink cells, indicating that GVR17 cells harbored a dominant cellular mutation that inhibited transformation by the v-fms oncogene. The revertant cells were refractory to retransformation by retroviruses containing v-fms or v-abl oncogenes, but could be transformed by v-ras-, v-raf-, and v-fes-containing retroviruses. Thus, the suppressing activity in GVR17 cells discriminates between transforming signals mediated by different tyrosine kinases and fails to block the transforming activity of two oncoproteins exhibiting either GTP-binding or serine/threonine kinase activity.

Animals↗
PubMed1983

Expression of c-onc genes: c-fos transcripts accumulate to high levels during development of mouse placenta, yolk sac and amnion.

The c-onc genes c-fos and c-fms are expressed at high levels specifically in mouse extra-embryonal tissues. Here, we report the results of a detailed analysis of expression of these genes within the developing placenta and extra-embryonal membranes (i.e., yolk sac and amnion). (i) The c-fos gene is expressed at relatively high, but nearly constant levels in the undissected placenta throughout gestation. (ii) The level of c-fos transcripts is greater than or equal to 15-fold higher in the separated outer portion of the midgestation placenta (primarily undifferentiated fetus-derived cytotrophoblast maternal decidua) relative to the inner moiety (predominantly differentiated syncytiotrophoblast). (iii) In the inner placenta and in the extra-embryonal membranes c-fos transcripts accumulate as gestation proceeds. The abundance of c-fos transcripts in the micro-surgically isolated 18th day amnion reaches a level which is two orders of magnitude greater than that in midgestation fetuses, and is thus close to the level of v-fos transcripts in virus-transformed cells. (iv) The distribution of c-fos transcripts within the developing extra-embryonal tissues is markedly different from that of the c-fms gene. It is suggested that the c-fos and c-fms proteins may participate in differentiation, growth or transport processes occurring in mouse extra-embryonal tissues.

Amnion↗
PubMed1996

Synergistic effects of transforming growth factor-beta on the expression of c-fms, macrophage colony-stimulating factor receptor gene, in vascular smooth muscle cells.

Vascular smooth muscle cells (SMC) transform to foam cells in the process of atherosclerosis. We have reported that SMC derived from the intima of atherosclerotic lesions express c-fms, macrophage colony-stimulating factor receptor gene, which is not normally expressed in medial SMC. In the present study, we demonstrated that transforming growth factor-beta (TGF-beta) synergistically induced expression of c-fms in the presence of platelet-derived growth factor-BB in human medial SMC, a level comparable to that observed in the intima. The induction of c-fms was not inhibited by protein kinase C (PKC) inhibitor, suggesting that TGF-beta induces c-fms via a PKC-independent pathway. These results suggest that TGF-beta plays an important role in the phenotypic change of smooth muscle cells to macrophage-like cells in the process of atherosclerosis.

Becaplermin↗
PubMed2003

Epigenetic consequences of AML1-ETO action at the human c-FMS locus.

Although many leukaemia-associated nuclear oncogenes are well characterized, little is known about the molecular details of how they alter gene expression. Here we examined transcription factor complexes and chromatin structure of the human c-FMS gene in normal and leukaemic cells. We demonstrate by in vivo footprinting and chromatin immunoprecipitation assays that this gene is bound by the transcription factor AML1 (RUNX1). In t(8;21) leukaemic cells expressing the aberrant fusion protein AML1-ETO, we demonstrate that this protein is part of a transcription factor complex binding to extended sequences of the c-FMS intronic regulatory region rather than the promoter. The AML1-ETO complex does not disrupt binding of other transcription factors, indicating that c-FMS is not irreversibly epigenetically silenced. However, AML1-ETO binding correlates with changes in the histone modification pattern and increased association of histone deacetylases. Our experiments provide for the first time a direct insight into the chromatin structure of an AML1-ETO-bound target gene.

Acute Disease↗
PubMed2026

Azacitidine-Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia.

BACKGROUND: Induction chemotherapy has long been a key component of curative therapy for fit patients with acute myeloid leukemia (AML), despite its frequently severe side effects and substantial health care utilization. For patients who are ineligible for induction chemotherapy, hypomethylating therapy plus venetoclax is the standard treatment owing to its efficacy and side-effect profile. METHODS: In this multicenter, phase 2 trial, we randomly assigned, in a 1:1 ratio, previously untreated adults with AML who were eligible for induction chemotherapy to receive either azacitidine plus venetoclax or induction chemotherapy. Patients with core binding factor fusions, mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3), or mutations in the gene encoding nucleophosmin-1 (NPM1; unless the patient was ≥60 years of age) were excluded. The primary end point was event-free survival. RESULTS: A total of 172 patients underwent randomization, with 86 patients assigned to each group. The median age of the patients was 64 years. A total of 72% of the patients had adverse-risk disease according to the European LeukemiaNet 2022 classification. At a median follow-up of 21.9 months, the median event-free survival was 14.5 months (95% confidence interval [CI], 10.4 to 24.4) in the azacitidine-venetoclax group, as compared with 6.2 months (95% CI, 4.1 to 10.1) in the induction chemotherapy group, corresponding to a hazard ratio for event or death of 0.57 (95% CI, 0.39 to 0.84; P = 0.002 by the stratified log-rank test). Infection of grade 3 or higher occurred in 28% of the patients (95% CI, 19 to 39) receiving azacitidine-venetoclax and in 41% of those (95% CI, 30 to 52) receiving induction chemotherapy; hemorrhage of grade 3 or higher occurred in 2% (95% CI, 0.3 to 8) and 12% (95% CI, 6 to 20), respectively. CONCLUSIONS: In this phase 2, randomized trial, azacitidine-venetoclax therapy led to significantly longer event-free survival than induction chemotherapy among induction-eligible patients with AML. (Funded by AbbVie and others; PARADIGM ClinicalTrials.gov number, NCT04801797.).

Adult↗
PubMedDate not supplied

Functional expressions of fms and M-CSF during trophoectodermal differentiation of human embryonal carcinoma cells.

A human embryonal carcinoma (EC) cell line, NCR-G3 (G3), is capable of differentiating into a variety of cell types in vitro, including epithelial, muscle, neural and trophoectodermal cells. The production of human chorionic gonadotropin (hCG), a trophoectoderm-specific hormone, begins 7 days after retinoic acid (RR1) treatment and peaks on day 12-13. In this study, we used G3 cells to investigate the biological significance of macrophage colony-stimulating factor (M-CSF), also called colony-stimulating factor-1 (CSF-1), and fms, a receptor tyrosine kinase for M-CSF. The mRNA of c-fms is constitutively expressed in both undifferentiated and differentiated G3 cells. Immunoprecipitation with anti-fms antibodies or flow cytometry revealed that differentiated G3 cells express fms on the cell surface. However, we were unable to demonstrate expression of fms on the surface of undifferentiated G3 cells. Expression of M-CSF mRNA and protein, however, was upregulated by RA treatment prior to hCG production. In order to investigate whether expression of both molecules is biologically functional in G3 cells, we conducted experiments using anti-M-CSF and fms antibodies with neutralizing activity and gene transfer to achieve over-expression of fms in G3 cells. As a result, we observed that hCG production following treatment with both neutralizing antibodies was more than 90 per cent inhibited, and that hCG production increased significantly as a result of over-expression of fms in G3 cells. Our results enabled us to show that M-CSF and fms play important functional roles in the differentiation of G3 cells into trophoectoderm. G3 cells are well suited to serve as an experimental model of human early embryogenesis and of placental differentiation.

Carcinoma, Embryonal↗
PubMed2003

Mutational analysis of class III receptor tyrosine kinases (C-KIT, C-FMS, FLT3) in idiopathic myelofibrosis.

Genomic DNA from patients with idiopathic myelofibrosis (IMF) was screened by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE) for mutations in the C-KIT gene (60 patients), as well as the C-FMS and FLT3 genes (40 patients). Intronic primers were used to amplify the entire coding region of both the C-KIT and C-FMS genes, and selected regions of the FLT3 gene. CSGE and direct DNA sequencing detected all previously reported as well as several novel polymorphisms in each of the genes. A novel c-fms exon 9 mutation (Gly413Ser) was detected in two patients. Its functional significance remains to be determined. The c-kit mutation Asp52Asn, previously described in two of six IMF patients in Japan, was not detected in this study. In addition, the reported c-fms mutations involving codons 301 and 969 were not identified. Therefore, in contrast to acute myeloid leukaemia, mutations in RTKs class III do not appear to play a significant pathogenetic role in idiopathic myelofibrosis.

DNA Mutational Analysis↗
PubMed1995

Influence of tyrosine residues Y705 and Y807 on the transforming potency of the v-fms oncogene product of feline sarcoma virus.

Cell transformation is characterized by overt changes in growth control and cell morphology. To study the role of tyrosine residues Y705 and Y807 of v-Fms of the McDonough strain of feline sarcoma virus in cell transformation we replaced them individually with phenylalanine residues. Cells expressing the mutant genes showed mitogenic properties similar to wild-type v-Fms transformed cells. However, the morphology of cells expressing the Y807F mutant remained the same as nontransformed cells. Four phosphoproteins of 190, 120, 55 and 50 kDa were detected in cells expressing the wild-type but were absent in cells expressing the mutant Y807F-v-fms gene.

Base Sequence↗
PubMed1994

Expression of c-fms on smooth muscle cells isolated from experimental arteriosclerosis.

In the present study, we demonstrated gene transcription of c-fms in smooth muscle cells isolated from an experimental rabbit model of arteriosclerosis (intimal smooth muscle cells), although there was no gene transcription of c-fms detected in medial smooth muscle cells. On immunocytochemical analysis, both types of smooth muscle cells similarly reacted with an antibody specific to muscle cells (HHF 35), but did not react with an antibody specific to rabbit macrophages (RAM 11). Intimal smooth muscle cells bound to acetylated LDL and resulting foam cell formation was observed. In response to M-CSF, an increased rate of cell proliferation was observed in intimal smooth muscle cells, but not in medial smooth muscle cells. These results indicated that intimal smooth muscle cells have monocyte-macrophages characteristics such as the expression of c-fms and scavenger receptor gene.

Animals↗
PubMed1988

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.

Animals↗
PubMed1989

A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma').

Two cases of non-Hodgkin's lymphoma are reported in which a chromosomal translocation was observed involving the same site (q35) on the long arm of chromosome 5. The other breakpoint involved in the translocation was chromosome 2 (p23) in one case and chromosome 3 (q12) in the other. Both cases were large cell lymphomas expressing CD30 antigen ('Ki-1 lymphoma'). One was clearly of T lymphoid origin, the other probably B cell derived. One other case of a Ki-1 lymphoma with 2;5 translocation (involving the same breakpoint on chromosome 5) has been reported previously, and it is suggested that this cytogenetic abnormality may be specifically associated with Ki-1 lymphoma. The literature contains a further eight cases of lymphoid neoplasms with a translocation involving a breakpoint at q35 on chromosome 5. They have all been described as cases of 'malignant histiocytosis', but the present findings make it likely that these cases were in reality also examples of Ki-1 lymphoma. The breakpoint at the q35 region on chromosome 5 is close to the position of the fms proto-oncogene, suggesting that an abnormality affecting this gene might possibly play a causal role in 'Ki-1 lymphoma'. However, DNA restriction fragment analysis of the present cases showed no evidence that the breakpoint on chromosome 5 involves the fms gene or its immediate vicinity.

Adolescent↗