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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma irradiation of plateau-phase clonal bone marrow stromal cell lines produces factor-independent growth of cocultivated clonal interleukin-3/granulocyte-macrophage colony-stimulating factor-dependent hematopoietic progenitor cell lines. The process is associated with three biologic changes including: (i) adherence of hematopoietic cells to stromal cells forming 'cobblestone islands'; (ii) an intermediate stage [during which the cells show proliferation in suspension in the presence in leukemogenic stromal factor (LSF), a factor similar to macrophage colony-stimulating factor (M-CSF) released by irradiated stromal cells, and transient hematopoietic cell surface expression of MAC-1, and c-fms (M-CSF receptor)]; and (iii) a third stage of factor-independence. A monoclonal antibody to M-CSF receptor inhibited proliferation of intermediate stage but not all factor-independent cell subclones. In the present studies, a subclonal factor-independent malignant subline of FDC-P1JL26 derived by cocultivation with gamma-irradiated stromal cells as well as the parent clone and intermediate stage cells were shown to express significant levels of M-CSF polyA+ mRNA and M-CSF of at least two sizes (23 and 15 kDa) as detected by 35S-methionine labelling and immunoprecipitation with polyclonal anti-M-CSF antiserum. There was no significant difference in intracellular M-CSF protein size between cells at each of the three stages of biologic change. This M-CSF was not detected on the cell surface by fluorescence-activated cell sorting (FACS). In contrast, c-fms expression at the cell surface was detected by FACS analysis and c-fms polyA+ mRNA was only detected during the intermediate stage of induction of factor-independence. FDC-P1JL26 parent cells, the subclone stimulated by LSF, and the factor-independent subclone, showed little or no detectable autophosphorylation of the c-fms receptor at tyrosine. There was no detectable rearrangement of the M-CSF or c-fms genes by Southern analysis between clonal lines during the three stages. While we cannot rule out an autocrine mechanism or mutated c-fms receptor mechanism, the data also suggest that evolution of hemopoietic cell factor-independence during cocultivation with irradiated stromal cells may involve a mechanism distal to the c-fms receptor/M-CSF interaction.
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PMID:Expression of M-CSF and its receptor (C-FMS) during factor-independent cell line evolution from hematopoietic progenitor cells cocultivated with gamma irradiated marrow stromal cell lines. 138 39

During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non-random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML-BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL-1 beta gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL-1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M-CSF gene and many of the same patients often had a simultaneous co-expression of the proto-oncogene c-fms which encodes for the M-CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M-CSF protein was documented in three of five patients studied. No significant interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.
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PMID:Constitutive expression of IL-1 beta, M-CSF and c-fms during the myeloid blastic phase of chronic myelogenous leukaemia. 153 85

In this report we show that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and rh macrophage (M)-CSF induce accumulation of interleukin-1 beta (IL-1 beta) mRNA in blood-derived mononuclear phagocytes (MNP). GM-CSF and M-CSF treatment of MNP is also associated with IL-1 beta secretion. Regulation of GM- and M-CSF-induced IL-1 beta mRNA expression involves transcriptional and posttranscriptional mechanisms. However, the action of IL-3 on synthesis of IL-1 beta mRNA differs from that of other CSFs: While GM-CSF and M-CSF induce binding activity of the nuclear factor (NF) kappa B, IL-3 treatment of MNP has no profound effect on NF kappa B binding to DNA. Moreover, IL-3 decreases the transcription rate of the IL-1 beta gene and has only little effect on stability of IL-1 beta mRNA, which is increased by GM- and M-CSF. However, IL-3 enhances M-CSF-induced accumulation of IL-1 beta mRNA by unknown posttranscriptional means that may relate to an increased expression of M-CSF receptor (ie, c-fms) mRNA, detectable in mononuclear phagocytes on exposure to IL-3.
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PMID:Interleukin-1 beta (IL-1 beta) expression in human blood mononuclear phagocytes is differentially regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, and IL-3. 1101 49

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
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PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

The lymphokine interleukin-3 (IL-3) promotes the growth and survival of immature hematopoietic cells. Previous studies have shown that IL-3 induces rapid increases in protein-tyrosine kinase (PTK) activity in IL-3--dependent cells. Unlike some other hematopoietic growth factor receptors (eg, c-fms and c-kit), however, the known subunits of the IL-3 receptor (IL-3R) lack intrinsic kinase activity. Recently, it was reported that the IL-2R (whose p75 beta-subunit shares sequence homology with a known murine IL-3R subunit and a common beta-subunit of the human IL-3R and granulocyte-macrophage colony-stimulating factor [GM-CSF] receptors) can physically associate with and regulate the activity of the SRC-family PTK, p56-LCK. Because most IL-3--dependent cells contain p53/56-LYN, but not p56-LCK, we explored the effects of IL-3 on the activities of LYN and other SRC-like PTKs in two human leukemic cell lines, AML-193 and TALL-101, which are phenotypically myeloid, and whose in vitro growth is dependent on IL-3. These cells expressed four of the eight known SRC-family proto-oncogenes: lyn, fyn, yes, and hck. When these factor-dependent leukemic cell lines were deprived of lymphokine to achieve cellular quiescence and then restimulated with IL-3, rapid increases (detectable within 1 minute and maximal by 10 minutes) were observed in the activity of the p53/56-LYN kinase, as assessed by in vitro kinase assays. In contrast, no alteration in the activities of other SRC-family PTKs present in these cells was detected after restimulation with IL-3 under the same conditions. This effect of IL-3 reflected an increase in the specific activity of the LYN kinase, because levels of the 53-Kd and 56-Kd LYN proteins were unaltered by IL-3 stimulation, as assessed by immunoblotting. Furthermore, the magnitude of these inducible increases in LYN kinase activity was dependent on the concentration of IL-3, and correlated with IL-3--induced proliferation. The IL-3--induced upregulation of LYN kinase activity may be mediated by the 120-Kd common subunit of the human IL-3 and GM-CSF receptors, because GM-CSF also stimulated marked increases in the activity of the LYN kinase, whereas granulocyte-CSF (G-CSF) did not, despite inducing cellular proliferation. These observations provide the first example of an IL-3--regulable PTK, and strongly suggest that the p53/56-LYN kinase participates in early IL-3--initiated signalling events, at least in some human leukemic cell lines.
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PMID:Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines. 163 19

Macrophage colony-stimulating factor (M-CSF) induces proliferation of monocyte/macrophage progenitor cells and can also activate some functions of mature cells including fetally derived placental cells. To study the role of M-CSF in the pregnant female reproductive tract, the expression of M-CSF mRNA and its receptor, c-fms proto-oncogene, in human placenta and decidua was identified. M-CSF and c-fms mRNAs, 4.7Kb and 3.9Kb respectively, were detected by Northern blotting in the early stage placenta and subsequently increased during pregnancy. These mRNAs were not detected in the nonpregnant endometrium but were strongly induced in maternal decidua with the same mRNA size as in the placenta. Northern blot hybridization on the endometrium of a pseudopregnant uterus revealed that the expression of endometrial M-CSF and c-fms mRNAs is regulated by synergistic action of female sex steroid hormones. These findings indicate that, in an autocrine and/or paracrine manner, M-CSF is deeply involved in the local proliferation and differentiation of cells at the materno-fetal interface, and support the placental immunotrophism hypothesis.
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PMID:Gene expression of macrophage colony-stimulating factor and its receptor in human placenta and decidua. 193 Jun 42

Protein tyrosine phosphorylation was studied in macrophages and fibroblasts to identify putative components of post-receptor mitogenic pathways that might be functionally conserved in different cell types. Nondenaturing conditions were established for the approximately quantitative recovery of anti-phosphotyrosine antibody (alpha PY)-reactive proteins from cells. A common, 57-kDa alpha PY-reactive protein was identified by V8 protease peptide mapping in colony-stimulating factor-1 (CSF-1)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated BAC1.2F5 macrophages, in platelet-derived growth factor-stimulated NIH-3T3 cells, and in CSF-1-stimulated NIH-3T3 cells expressing the c-fms/CSF-1 receptor. The 57-kDa protein was phosphorylated on serine and tyrosine and was the only alpha PY-reactive protein band whose phosphorylation was reproducibly increased in GM-CSF-stimulated cells. The effect of the growth factors on the tyrosine phosphorylation of the 57-kDa protein could be mimicked by treatment of the cells with orthovanadate, a phosphotyrosine protein phosphatase inhibitor. In the absence of growth factors, tyrosine phosphorylation of the 57-kDa protein was higher in v-fms or c-fms (F969, S301)-transformed NIH-3T3 cells than in untransformed NIH-3T3 (c-fms) and NIH-3T3 (c-fms, F969) cells. These data indicate that the 57-kDa protein is a common target for growth factor-stimulated tyrosine phosphorylation and potentially important for growth factor mitogenic signaling.
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PMID:Tyrosine phosphorylation of a common 57-kDa protein in growth factor-stimulated and -transformed cells. 170 76

There are clones of myeloid leukemic cells that can be induced to undergo terminal cell differentiation to macrophages by normal hemopoietic regulatory proteins. Induction of differentiation in two different clones of myeloid leukemic cells with interleukin 6 (IL-6) or granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in induction of mRNA for the hemopoietic regulatory proteins IL-6, GM-CSF, interleukin 1 alpha and interleukin 1 beta, tumor necrosis factor, and transforming growth factor beta 1. In one of these clones, induction of differentiation with GM-CSF was also associated with induction of mRNA for macrophage colony-stimulating factor (M-CSF) but not for the receptor for M-CSF (c-fms), whereas in the other clone, induction of differentiation with IL-6 was associated with induction of mRNA for both c-fms and M-CSF. The clones also differed in their responsiveness to these regulators. There was no induction of mRNA for granulocyte colony-stimulating factor or interleukin 3 during differentiation of either clone. The results indicate that the genes for a nearly normal network of positive and negative hemopoietic regulatory proteins are induced during differentiation of these myeloid leukemic cells and that there are leukemic clones with specific defects in this network.
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PMID:The network of hemopoietic regulatory proteins in myeloid cell differentiation. 175 9

Progestins have biological effects of regression and differentiation on human endometrial adenocarcinoma. We investigated the effects of progestin on the induction of macrophage-colony-stimulating factor (M-CSF) and its receptor messenger RNAs in the human endometrial adenocarcinoma cell line Ishikawa which has receptors for both estrogen and progesterone. Poly(A)+RNA extracted from Ishikawa cells cultured with or without synthetic progestin R5020 was subjected to Northern blot hybridization using M-CSF and c-fms cDNA probes. The expression of M-CSF mRNA in Ishikawa cells increased about 2.3 times following treatment with R5020 at 10(-7) M. Induction of M-CSF mRNA by R5020 was antagonized by anti-progestin RU486 in a dose-dependent manner. However, c-fms mRNA, coding the M-CSF receptor, was expressed constitutively in Ishikawa cells and its expression was not affected by hormonal treatment. We further examined the biological effects of M-CSF on endometrial cancer cells. Colony formation of Ishikawa cells in soft agar, which represents anchorage-independent cell growth, was inhibited by M-CSF treatment. On the other hand, accumulation of glycogen granules in cytoplasm detected by periodicacid-Schiff staining was observed in Ishikawa cells treated with M-CSF. These results indicate that M-CSF, whose gene expression was enhanced by progestin, suppressed growth and induced differentiation of endometrial adenocarcinoma cells. These effects of M-CSF on endometrial cancer cells are similar to those of progestins, so the effects of progestins on these cells are, at least in part, probably mediated by M-CSF in an autocrine or paracrine manner.
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PMID:The biological effects of macrophage-colony-stimulating factor induced by progestin on growth and differentiation of endometrial adenocarcinoma cells. 183 4

Colony-stimulating factor-1 (CSF-1), a growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells, has been implicated in the functional regulation and growth of the murine placenta through the presence of the CSF-1 receptor, c-fms, found in this tissue. In this study we examined the tissue levels of CSF-1 by RIA and the relative expression of CSF-1 and c-fms mRNA by Northern blot analysis in human endometrial, decidual, and placental tissues during the normal menstrual cycle and early pregnancy. All endometrial, decidual, and placental tissues demonstrated extractable immunoreactive CSF-1 and expressed the 4.0-kilobase CSF-1 mRNA species. First trimester decidual tissue expressed higher levels of CSF-1 mRNA than proliferative (3.2-fold higher; P less than 0.01) or secretory (2.4-fold higher; P less than 0.01) endometrial tissues, whereas proliferative and secretory endometrial tissues expressed similar levels of CSF-1 mRNA. Tissue extractable levels of immunoreactive CSF-1 were 3.2-fold (P less than 0.05) higher in first trimester decidual tissue and 2.9-fold (P less than 0.05) higher in secretory endometrial tissue compared to levels in proliferative endometrial tissue, whereas first trimester decidua and secretory endometrial tissues had similar levels of immunoreactive CSF-1. There was expression of c-fms mRNA in all endometrial and first trimester decidual tissue samples, with little change during the menstrual cycle and early pregnancy. In placenta, there was a positive correlation of increasing CSF-1 and c-fms mRNA expression with increasing gestational age. These results suggest that there is increased local production of CSF-1 in tissues found at the maternal-fetal interface during the time of implantation and early pregnancy. This increased production of CSF-1 may play a role in decidual function and placental growth through the presence of c-fms in these tissues.
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PMID:Colony-stimulating factor-1 and c-fms expression in human endometrial tissues and placenta during the menstrual cycle and early pregnancy. 183 23


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