SEARCH · PubMed Health

Results for “Genes, fms”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 37 records · Page 2Linked to original sources

PubMed2001

A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression.

The c-fms gene encodes the receptor for macrophage colony-stimulating factor-1. This gene is expressed selectively in the macrophage cell lineage. Previous studies have implicated sequences in intron 2 that control transcript elongation in tissue-specific and regulated expression of c-fms. Four macrophage-specific deoxyribonuclease I (DNase I)-hypersensitive sites (DHSs) were identified within mouse intron 2. Sequences of these DHSs were found to be highly conserved compared with those in the human gene. A 250-bp region we refer to as the fms intronic regulatory element (FIRE), which is even more highly conserved than the c-fms proximal promoter, contains many consensus binding sites for macrophage-expressed transcription factors including Sp1, PU.1, and C/EBP. FIRE was found to act as a macrophage-specific enhancer and as a promoter with an antisense orientation preference in transient transfections. In stable transfections of the macrophage line RAW264, as well as in clones selected for high- and low-level c-fms mRNA expression, the presence of intron 2 increased the frequency and level of expression of reporter genes compared with those attained using the promoter alone. Removal of FIRE abolished reporter gene expression, revealing a suppressive activity in the remaining intronic sequences. Hence, FIRE is shown to be a key regulatory element in the fms gene.

3T3 Cells↗

PubMed2004

Repression of the c-fms gene in fibroblast cells by c-Myc-MM-1-TIF1beta complex.

MM-1 has been reported to repress the E-box-dependent transcription activity of c-Myc by recruiting histone deacetylase 1 complex via TIF1beta/KAP1. In this study, to identify target genes for c-Myc-MM-1-TIF1beta, we established rat-1 cells harboring the dominant-negative form of TIF1beta to abrogate the pathway from TIF1beta to MM-1-c-Myc. This cell line, in which transcription activity of c-Myc was activated, was found to be tumorigenic. By DNA-microarray analysis of this cell line, expression and promoter activity of the c-fms oncogene were found to be upregulated. Of the two promoters, pE1 and pE2, in the c-fms gene, pE1 promoter activity was found to be activated in an E-box-dependent manner.

Animals↗

PubMed1988

Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells.

Macrophage colony-stimulating factor (CSF-1; M-CSF) is a growth factor required for growth and differentiation of mononuclear phagocytes. The effects of CSF-1 are mediated through binding to specific, high-affinity surface receptors encoded by the c-fms gene. CSF-1 and c-fms gene expression was investigated in fresh human acute myeloblastic leukemic cells by Northern blot hybridization using cDNA probes. 4.0-kb CSF-1 transcripts were detected in 10 of 17 cases of acute myeloblastic leukemia (AML), while c-fms transcripts were detected in 7 of 15. Coexpression of CSF-1 and c-fms was observed in five cases, and in five other cases neither gene was expressed. In situ hybridization demonstrated that transcripts for CSF-1 were present in 70-90% of cells in each of three cases studied while c-fms mRNA was detected in 40-70% of cells. The constitutive expression of CSF-1 transcripts was associated with production of CSF-1 protein, although detectable amounts of CSF-1 were not secreted unless the cells were exposed to phorbol ester. These results demonstrate that leukemic myeloblasts from a subset of patients with AML express transcripts for both the CSF-1 and CSF-1 receptor genes, often in the same leukemic cells in vitro.

Colony-Stimulating Factors↗

PubMed1994

Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes.

The receptor for macrophage colony stimulating factor (CSF-1), the c-fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c-ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms proximal promoter. On the other hand c-myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-fms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c-myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-fms mRNA. The repressor function of c-myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-fms and that c-myb acts to ensure correct temporal expression of c-fms during myeloid differentiation.

3T3 Cells↗

PubMed1992

Lineage-specific methylation of the c-fms gene in blood cells and macrophages.

DNA methylation belongs to the multilevel genetic control system regulating differentiation processes and gene expression. The extent to which DNA methylation contributes to the differentiation of hematopoietic cells is elusive. In the present study we investigated the methylation state of the c-fms/M-CSF receptor gene in normal human blood cells and tissue macrophages. The methylation pattern of the c-fms gene as detected by isoschizomeric restriction analysis with MspI/HpaII showed only slight interindividual variations in normal donors, whereas constant differences were found between granulocytes and monocytes from the same donor. The second intron of the c-fms gene contains several CpG loci which were found to be hypomethylated on both alleles in monocytes and tissue macrophages. By contrast, these positions were methylated in granulocytes and lymphocytes that did not express the c-fms gene. In comparison to monocytes alveolar and peritoneal macrophages revealed an enhanced demethylation. There were constant differences in c-fms gene methylation between alveolar and peritoneal macrophages with a higher degree of demethylation in alveolar macrophages. We conclude that c-fms gene demethylation is involved in the differentiation of monocytes and macrophages from immature precursors and that the demethylation of lineage-specific growth factor receptor genes might provide an important step in lineage commitment of hematopoietic cells.

Alleles↗

PubMed1990

Mutation of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia.

We studied 41 patients with myelodysplastic syndromes or acute myeloid leukemia to assess the presence of point mutations in the human FMS gene (M-CSF receptor). Using the polymerase chain reaction and hybridization of oligonucleotide probes to the amplified sequences, we have detected mutations in eight of 41 patients, at codons 301 and 969. In vitro work has highlighted mutations at these codons as being oncogenic. We now report the detection of potentially activating mutations of the human FMS gene in vivo. The consequence of these mutations in the multistep pathogenesis of myeloid malignancy and their relevance to prognosis remains to be determined.

Alleles↗

PubMed1989

Downregulation of c-fms gene expression in human monocytes treated with phorbol esters and colony-stimulating factor 1.

The colony-stimulating factor-1 (CSF-1) regulates survival, growth, and differentiation of monocytes by binding to a single class of high-affinity receptors. The CSF-1 receptor is identical to the product of the c-fms protooncogene. The present studies monitored the effects of TPA and CSF-1 on c-fms gene expression in human monocytes. The results demonstrate that TPA downmodulates the constitutive expression of c-fms mRNA to low but detectable levels. Treatment of human monocytes with TPA was similarly associated with decreases in levels of the 138- and 125-Kd c-fms-encoded proteins. However, the kinetics of c-fms protein downmodulation indicated independent effects of TPA on c-fms expression at the RNA and protein levels. Furthermore, c-fms protein levels subsequently recovered despite persistently low levels of c-fms mRNA. Although previous studies demonstrated that c-fms protein is down-regulated in the presence of CSF-1, the present results indicate that CSF-1 also downregulates levels of c-fms mRNA. Moreover, the results indicate that CSF-1 increases protein kinase C activity in the membrane fraction. Together, these findings suggest that c-fms gene expression is differentially regulated at both the RNA and protein levels after activation of protein kinase C in human monocytes treated with TPA and CSF-1.

Blotting, Northern↗

PubMed2004

[Deletional polymorphism of the 11th intron of the human c-fms gene: allele frequency in certain Russian populations and possible functional significance].

Analysis of deletion polymorphism of human c-fms gene intron 11 (approximately 425-bp deletion) is of particular interest because of the increased proportion of the deletion heterozygotes among the infants born from the parents, one of which lacks the deletion allele, and the other is heterozygous for the deletion. In this study, allele and haplotype frequencies of the polymorphism examined were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy-Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the context analysis of DNA of the deleted fragment along with the flanking sequences that this region contained a number of transcription factor motifs (Ets, SRF, and Myc), potentially capable of the regulation of the M-CFF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that allele lacking the fragment of intron 11 could be restricted in its ability to modulate the level of the c-fms transcription in response to the action of M-CSF. The data of molecular epidemiological survey serve as the indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples of acute bronchitis and trichomoniasis patients allelic and genotype frequencies were statistically significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample.

Base Sequence↗

PubMed1989

Induction of macrophage colony-stimulating factor-dependent growth and differentiation after introduction of the murine c-fms gene into FDC-P1 cells.

A system has been established for analyzing the functions of the c-fms/macrophage colony-stimulating factor (M-CSF) receptor gene product in hematopoietic growth and differentiation. The murine c-fms gene was introduced into the factor-dependent murine hematopoietic cell line FDC-P1 by retroviral infection, and conversion to M-CSF-dependent growth was assayed in agar cultures. Expression of the c-fms gene in FDC-P1 cells, which normally do not express this gene, resulted in the conversion of resultant FD(c-fms) cells to M-CSF-dependent growth. Stimulation of FD(c-fms) cells by M-CSF led to the formation of colonies of altered morphology and produced reversible morphological changes suggestive of myeloid differentiation. M-CSF also induced expression of mature myeloid surface marker proteins in the FD(c-fms) cells. Neither multi-CSF nor granulocyte-macrophage CSF induced similar phenotypic changes but remained able to stimulate the proliferation of undifferentiated FD(c-fms) cells. These results indicate that the c-fms gene was expressed functionally in FDC-P1 cells and transmitted signals for growth. Also, the interaction of M-CSF with the c-fms gene product generated an additional signal for myeloid differentiation but did not irreversibly commit FD(c-fms) cells to terminal differentiation. This system can be used for molecular analysis of the growth- and differentiation-promoting activities of the c-fms proto-oncogene.

Cell Differentiation↗

PubMed1989

Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes.

Structural analysis of the 5' end of the human c-fms gene revealed that a large intron of about 25 kilobases separates an upstream noncoding exon (exon 1) from the signal peptide-containing exon (exon 2). Northern (RNA) blot analysis, S1 nuclease mapping, and primer extensions showed that exon 1 is transcribed in placenta but not in cells of the monocytic lineage. This is due to the differential usage of promoters, separated by approximately 25 kilobases, in a cell-specific manner. One major c-fms transcript was observed in U-937 cells, whereas multiple initiation sites for transcription appeared to be utilized in placental cells. Nucleotide sequence comparisons showed that the 3' end of the human platelet-derived growth factor receptor gene lies approximately 350 base pairs upstream of the major initiation sites for c-fms transcription in placental trophoblasts.

Amino Acid Sequence↗

PubMed2000

An orthologue of the kit-related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio.

Developmental mechanisms underlying traits expressed in larval and adult vertebrates remain largely unknown. Pigment patterns of fishes provide an opportunity to identify genes and cell behaviors required for postembryonic morphogenesis and differentiation. In the zebrafish, Danio rerio, pigment patterns reflect the spatial arrangements of three classes of neural crest-derived pigment cells: black melanocytes, yellow xanthophores and silver iridophores. We show that the D. rerio pigment pattern mutant panther ablates xanthophores in embryos and adults and has defects in the development of the adult pattern of melanocyte stripes. We find that panther corresponds to an orthologue of the c-fms gene, which encodes a type III receptor tyrosine kinase and is the closest known homologue of the previously identified pigment pattern gene, kit. In mouse, fms is essential for the development of macrophage and osteoclast lineages and has not been implicated in neural crest or pigment cell development. In contrast, our analyses demonstrate that fms is expressed and required by D. rerio xanthophore precursors and that fms promotes the normal patterning of melanocyte death and migration during adult stripe formation. Finally, we show that fms is required for the appearance of a late developing, kit-independent subpopulation of adult melanocytes. These findings reveal an unexpected role for fms in pigment pattern development and demonstrate that parallel neural crest-derived pigment cell populations depend on the activities of two essentially paralogous genes, kit and fms.

Animals↗

PubMed1986

Appropriate glycosylation of the fms gene product is a prerequisite for its transforming potency.

Processing inhibitors of N-linked glycans were used to determine whether correct glycosylation of the oncogene product gp140v-fms, encoded by the McDonough strain of feline sarcoma virus (SM-FeSV), is required to maintain the oncogenic properties of v-fms. SM-FeSV-transformed cells treated with the glucosidase-I inhibitors N-methyldeoxynojirimycin (MdN) or castanospermine synthesized predominantly a gp125v-fms species which had a normal half life. The molecule was transported to the plasma membrane and exhibited normal kinase activity as determined by autophosphorylation. However, although no significant change in cell morphology of the SM-FeSV-transformed cells was observed in the presence of castanospermine, growth of these cells became strictly serum-dependent. In addition, growth in soft agar was drastically retarded despite the presence of 10% calf serum, indicating that the transformed properties of the cells were altered. In contrast, swainsonine, an inhibitor of the processing alpha-mannosidase-II, had no effect. Cells transformed by the Snyder Theilen strain of FeSV were used to demonstrate that the altered proliferative properties were directly linked to the modified structure of the fms gene product. Our data suggest that the extracellular domain of gp140v-fms plays a role in regulating cell proliferation.

Alkaloids↗

PubMed1988

CSF-1 and C-FMS gene expression in human carcinoma cell lines.

The macrophage-specific colony stimulating factor CSF-1 is required for the growth and differentiation of monocytes. The cell surface receptor for CSF-1 is identical to the product of the c-fms proto-oncogene. The present studies have monitored CSF-1 and c-fms expression in human carcinoma cell lines. Two of three human ovarian carcinoma cell-lines expressed multiple species of CSF-1 mRNA. Furthermore, detection of CSF-1 transcripts was associated with secretion of CSF-1 protein that was increased after phorbol ester treatment. CSF-1 mRNA was also detectable in 4 breast and 2 lung carcinoma cell lines. In contrast, c-fms expression was found only in SK-Br-3 breast carcinoma cells. Similar studies in 2 human choriocarcinoma cell lines demonstrated the presence of c-fms, but not CSF-1, transcripts. While phorbol ester treatment was associated with increased c-fms mRNA levels in choriocarcinoma cells, this agent had no effect on CSF-1 expression. These findings indicate that: 1) CSF-1 expression is frequent in human ovarian, breast and lung carcinoma cells; and 2) coexpression of the CSF-1 and c-fms genes, as found in monocytes is infrequent in malignant epithelial and choriocarcinoma cell lines.

Blotting, Northern↗

PubMed2006

Lack of TP53 and FMS gene mutations in children with myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are rare disorders in children. Molecular mechanisms underlying MDS in children are not yet completely understood. Considering the role of FMS and TP53 gene mutations in adult MDS patients, we analyzed mutations of these genes in a cohort of 35 children with MDS. Single-strand conformation polymorphism polymerase chain reaction analysis performed on FMS codon 969 and TP53 exons 5-9 showed no mutations in the analyzed sequences. Our results suggest that molecular mechanisms of MDS evolution in children are different from those in adults.

Child, Preschool↗

PubMed1991

The c-fms gene complements the mitogenic defect in mast cells derived from mutant W mice but not mi (microphthalmia) mice.

Mutations at three loci in the mouse--W, Steel Sl), and microphthalmia (mi)--can lead to a deficiency in melanocytes and mast cells. As well, W and Sl mutants can be anemic and sterile, whereas mi mice are osteopetrotic due to a monocyte/macrophage defect. Recent data have shown that the c-kit receptor tyrosine kinase is the gene product of the W locus, whereas Sl encodes the ligand for this growth factor receptor. We show here that ectopic expression of c-fms, a gene that encodes a macrophage growth factor receptor that is closely related to the c-kit receptor, complements mutations at the W locus in an in vitro mast cell/fibroblast coculture system but is unable to reverse the inability of mi/mi mast cells to survive under these conditions. Furthermore, mast cells expressing the c-fms receptor survive on a monolayer of fibroblasts homozygous for the Sl mutation. These results suggest that ligand binding to the c-kit or c-fms receptor activates identical or overlapping signal transduction pathways. Furthermore, they suggest that mi encodes a protein necessary for transducing signals mediated by way of either the c-kit or c-fms receptor.

Animals↗

PubMed2006

The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction.

The transcription factor Pax5 (BSAP) is required for the expression of a B-cell-specific genetic program and for B-cell differentiation, and also to suppress genes of alternative lineages. The molecular mechanism by which repression of myeloid genes occurs during early B-lineage restriction is unknown and in this study we addressed this question. One of the genes repressed by Pax5 in B cells is the colony-stimulating factor receptor 1 gene (csf1r or c-fms). We examined the changes in chromatin caused by Pax5 activity, and we show that Pax5 is directly recruited to c-fms resulting in the rapid loss of RNA polymerase II binding, followed by loss of transcription factor binding and DNaseI hypersensitivity at all cis-regulatory elements. We also show that Pax5 targets the basal transcription machinery of c-fms by interacting with a binding site within the major transcription start sites. Our results support a model by which Pax5 does not lead to major alterations in chromatin modification, but inhibits transcription by interfering with the action of myeloid transcription factors.

Animals↗

PubMed1985

Restriction fragment length polymorphism of the human c-fms gene.

By using blot hybridization with a v-fms probe, a polymorphism for EcoRI, HindIII, and BamHI restriction endonuclease sites associated with the human c-fms locus was observed in a random adult population. This restriction fragment length polymorphism can be explained on the basis of the existence of two alleles, a and b, and is due to a short (congruent to 500 base pairs) deletion characteristic of allele a. The distribution in the analyzed population (48 unrelated individuals) is 23% heterozygotes ab, 75% homozygotes bb, and 2% homozygotes aa. Though the inheritance of this polymorphism follows a Mendelian pattern, the children from couples ab X bb are of the following genotype: 74% ab and 26% bb. These deviations from the expected frequencies of 50% suggest a selective pressure in favor of heterozygotes.

Alleles↗

PubMed2002

Heat shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes.

Heat shock factor 1 (HSF1), in addition to its pivotal role as a regulator of the heat shock response, functions as a versatile gene repressor. We have investigated the structural domains involved in gene repression using mutational analysis of the hsf1 gene. Our studies indicate that HSF1 contains two adjacent sequences located within the N-terminal half of the protein that mediate the repression of c-fos and c-fms. One region (NF) appears to be involved in quenching transcriptional activation factors on target promoters and binds to the basic zipper transcription factor NF-IL6 required for activation of c-fms and IL-1beta. The NF domain encompasses the leucine zipper 1 and 2 sequences as well as the linker domain between the DNA binding and leucine zipper regions. The function of this domain in gene repression is highly specific for HSF1, and the homologous region from conserved family member HSF2 does not restore repressive function in HSF2/HSF1 chimeras. In addition, HSF2 is not capable of binding to NF-IL6. The NF domain, although necessary for repression, is not sufficient, and a second region (REP) occupying a portion of the regulatory domain is required for repression. Neither domain functions independently, and both are required for repression. Furthermore, we constructed dominant inhibitors of c-fos repression by HSF1, which also blocked the repression of c-fms and IL-1beta, suggesting a shared mechanism for repression of these genes by HSF1. Our studies suggest a complex mechanism for gene repression by HSF1 involving the binding to and quenching of activating factors on target promoters. Mapping the structural domains involved in this process should permit further characterization of molecular mechanisms that mediate repression.

Animals↗