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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)

Bcl-3 is a proto-oncogene involved in the chromosomal translocation t(14;19) found in some patients with chronic lymphocytic leukemia. It shares structural similarities with and is a member of the IkappaB family of proteins. In this report, involvement of Bcl-3 in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined. In TF-1 cells, an erythroleukemia cell line, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) greatly enhanced Bcl-3 expression at both the protein and mRNA levels in association with stimulation of proliferation. Bcl-3 protein was also highly expressed in early burst-forming unit-erythroid (BFU-E)-derived erythroid precursors (day 7) and decreased during maturation (days 10 and 14), suggesting that Bcl-3 is involved in normal erythroid proliferation. In these hematopoietic cells, Bcl-3 was hyperphosphorylated. GM-CSF and Epo modulated the subcellular localization of Bcl-3. Upon stimulation of TF-1 cells with GM-CSF or Epo, the nuclear translocation of Bcl-3 was dramatically enhanced. Overexpression of Bcl-3 in TF-1 cells by transient transfection along with the NF-kappaB factors p50 or p52 resulted in significant induction of an human immunodeficiency virus-type 1 (HIV-1) kappaB-TATA-luceriferase reporter plasmid, demonstrating that Bcl-3 has a positive role in transactivation of kappaB-containing genes in erythroid cells. Stimulation with GM-CSF enhanced c-myb mRNA expression in these cells. Bcl-3 in nuclear extracts of TF-1 cells bound to a kappaB enhancer in the c-myb promoter together with NF-kappaB2/p52 and this binding activity was enhanced by GM-CSF stimulation. Furthermore, cotransfection of Bcl-3 with p52 or p50 in TF-1 cells resulted in significant activation of a c-myb kappaB-TATA-luceriferase reporter plasmid. These findings suggest that Bcl-3 may participate in the transcriptional regulation of certain kappaB-containing genes involved in hematopoiesis, including c-myb.
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PMID:Bcl-3 expression and nuclear translocation are induced by granulocyte-macrophage colony-stimulating factor and erythropoietin in proliferating human erythroid precursors. 969 11

We previously have shown that the zinc finger transcription factor Egr-1 blocked granulocytic differentiation of HL-60 cells, restricting differentiation along the monocytic lineage. Egr-1 also was observed to block granulocyte colony-stimulating factor (G-CSF)-induced differentiation of interleukin-3 (IL-3)-dependent 32Dcl3 hematopoietic precursor cells, endowing the cells with the ability to be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) for terminal differentiation along the macrophage lineage. To better understand the function of Egr-1 as a positive modulator of monocytic differentiation, in this work we have studied the effect of ectopic expression of Egr-1 on the murine myeloblastic leukemic cell line M1, which is induced for differentiation by the physiological inducer IL-6. It is shown that, unlike in HL-60 and 32Dcl3 cells, ectopic expression of Egr-1 in M1 cells resulted in activation of the macrophage differentiation program in the absence of differentiation inducer. This included the appearance of morphologically differentiated cells, decreased growth rate in mass culture, and cloning efficiency in soft agar, and expression of endogenous c-myb and c-myc mRNAs was markedly downregulated. Untreated M1Egr-1 cells also exhibited cell adherence, expression of Fc and C3 receptors, and upregulation of the myeloid differentiation primary response genes c-Jun, junD, and junB and the late genetic markers ferritin light-chain and lysozyme. Ectopic expression of Egr-1 in M1 cells also dramatically increased the sensitivity of the cells for IL-6-induced differentiation, allowed a higher proportion of M1 cells to become terminally differentiated under conditions of optimal stimulation for differentiation, and decreased M1 leukemogenicity in vivo. These findings demonstrate that the functions of Egr-1 as a positive modulator of macrophage differentiation vary, depending on the state of lineage commitment for differentiation of the hematopoietic cell type.
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PMID:The zinc finger transcription factor Egr-1 activates macrophage differentiation in M1 myeloblastic leukemia cells. 973 Oct 53

The intestinal epithelium is a continuously renewing tissue. In the colon, stem cells are maintained at the base of highly organized crypts, where they undergo asymmetric division and give rise to daughter cells that proliferate and migrate up the crypt as they differentiate, then become senescent and are finally shed into the intestinal lumen. The growth factor requirements of fetal and prenatal colon cells for colony formation and that influence the establishment of cell lines from Immorto-mouse (Charles River, Wilmington, MA) transgenic embryos were explored. Single cell suspensions were isolated and cultured in a large range of growth factor combinations and conditions to determine their growth properties in soft agar. We report an important advance in the culture of mouse colonocytes by using macrophage colony-stimulating factor (CSF-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF). A substantial proportion of colonies grown under low oxygen tension in the presence of CSF-1 and GM-CSF express intestinal epithelial A33 antigen, have the expected gene expression profile, including c-fms and transcription factor c-myb, and show an appropriate epithelial cell morphology and undetectable CD45. Confocal microscopy on isolated crypts displays basolateral expression of c-Fms and E-cadherin on most epithelial cells. Fetal colon cultures from the Immorto-mouse with CSF-1 produced rapid outgrowth and readily established cell lines, in contrast to cultures without CSF-1. These observations have implications for the understanding of colon epithelial development and recovery following cytotoxic damage as well as providing a basis for the observation that some colon (and other epithelial) tumor cells respond to CSF-1 and GM-CSF.
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PMID:Colony-stimulating factor-1 promotes clonogenic growth of normal murine colonic crypt epithelial cells in vitro. 1529 53


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