Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q15744 (C/EBP epsilon)
 82 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C/EBP epsilon is a recently cloned member of the C/EBP family of transcriptional factors. Previous studies demonstrated that the expression of this gene is tightly regulated in a tissue specific manner; it is expressed exclusively in myeloid cells. C/EBP epsilon-deficient mice developed normally but failed to generate functional neutrophils and eosinophils, and these mice died of opportunistic infections suggesting that C/EBP epsilon may play a central role in myeloid differentiation. To identify myelomonocytic genes regulated by the C/EBP epsilon gene, we performed representational difference analysis (RDA), a polymerase chain reaction (PCR)-based subtractive hybridization using neutrophils and macrophages from wild-type and C/EBP epsilon knockout mice. We identified a set of differentially expressed genes, including chemokines specific to myelomonocytic cells. Several novel genes were identified that were differentially expressed in normal myelomonocytic cells. Taken together, we have found several genes whose expression might be enhanced by C/EBP epsilon. (Blood. 2000;96:3953-3957)
Blood 2000 Dec 01
PMID:Representational difference analysis using myeloid cells from C/EBP epsilon deletional mice. 1109 83

Internal tandem duplication (ITD) mutations of the juxtamembrane domain-coding sequence of the FLT3 gene are found in up to 34% of patients with acute myeloid leukemia (AML) and are associated with a poor prognosis. FLT3/ITDs result in constitutive activation of the tyrosine kinase domain and transform growth factor-dependent cell lines. FLT3 activation leads to antiapoptotic and proliferative signals, but little is known about the impact of FLT3/ITDs on differentiation. This study was designed to investigate the effect of FLT3/ITD expression on the differentiation of the 32Dcl3 (32D) myeloblastic cell line to neutrophils in response to granulocyte colony-stimulating factor (G-CSF). Expression of FLT3/ITD completely blocked morphologic differentiation and induction of myeloperoxidase (MPO), lysozyme, and CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) in response to G-CSF. Wild-type FLT3 and vector-transfected 32D cells were able to differentiate, although the maturation of FLT3-transfected cells was delayed by FLT3 ligand (FL) stimulation. CEP-701, a potent FLT3 tyrosine kinase inhibitor, overcame the morphologic block in differentiation caused by FLT3/ITD expression and allowed G-CSF induction of myeloid maturation markers. These findings suggest that blocking differentiation may be one of the mechanisms by which FLT3/ITDs contribute to leukemogenesis. CEP-701 and other FLT3 inhibitors may be useful for overcoming the block to differentiation (as well as the block to apoptosis) in the leukemic cells of patients with AML.
Blood 2002 Dec 01
PMID:Targeted inhibition of FLT3 overcomes the block to myeloid differentiation in 32Dcl3 cells caused by expression of FLT3/ITD mutations. 1239 74

The characteristics of human resistin (RETN) are unclear and controversial despite intensive adipose-focused research. Its transcriptional and functional similarity with the murine myeloid-specific and CCAAT/enhancer binding protein epsilon (Cebpe)-dependent gene, resistin-like gamma (Retnlg), is unexplored. We examined the human CEBPE-regulatory pathway by unbiased reference and custom gene expression assays. Real-time RT-PCR analysis demonstrated lack of both the transcriptional factor CEBPE and RETN expression in adipose and muscle cells. In contrast, primary myelocytic samples revealed a concerted CEBPE-RETN transcription that was significantly elevated in inflammatory synoviocytes relative to intact peripheral blood mononuclear cells (PBMC). Mouse Cebpe and Retnlg were predictably expressed in macrophages, whereas Retn was abundant in adipocytes. Quite the opposite, a low and inconsistent RETN transcription was seen in some human white adipose tissue (WAT) biopsies without any relationship to body mass index, insulin sensitivity, or fat depot. However, in these cases, RETN was co-detected with CEBPE and the leukocyte-specific marker, EMR1, indicating the presence of inflammatory cells and their possible resistin-mediated effect on adipocytes. Indeed, addition of human resistin to WAT in culture induced, like in PBMC, the inflammatory cytokines IL6, IL8 and TNF. Importantly, the expression of the adipose-specific markers CEBPA, FABP4 and SLC2A4 was unchanged, while the expected inhibitory effect was seen with TNF. Both cytokines increased the mRNA level of CCL2 and MMP3, which may further promote inflammation in WAT. Thus, the myeloid-restricted nature of CEBPE precludes the expression of RETN in human adipocytes which, however, are targeted by this innate immune-derived proinflammatory cytokine.
PLoS One 2006 Dec 20
PMID:Human resistin is a systemic immune-derived proinflammatory cytokine targeting both leukocytes and adipocytes. 1718 59

Treatment of acute promyelocytic leukemia with retinoic acid (RA) results in differentiation of the leukemic cells and clinical remission. However, the cellular factors that regulate RA-induced myeloid differentiation are largely unknown, and other forms of acute myelogenous leukemia (AML) do not respond to this differentiation therapy. A greater understanding of the molecules that positively or negatively regulate RA-induced differentiation should facilitate the development of more effective differentiation therapies. In this study, we investigated the potential role of Src family kinases (SFK) in the regulation of RA-induced gene expression and myeloid differentiation. We report that inhibition of SFKs markedly enhanced RA-induced differentiation in myeloid cell lines and primary AML cells, as assessed by flow-cytometric analysis of cell surface markers, morphologic analysis, and nitroblue tetrazolium reduction. In addition, inhibition of SFKs enhanced expression from retinoic acid receptor (RAR) target genes encoding CCAAT/enhancer binding protein epsilon (C/EBPepsilon), PU.1, intercellular adhesion molecule-1 (ICAM-1), and cathepsin D. Moreover, a constitutively active Src inhibited RAR-dependent transcription, whereas a kinase-dead Src exerted little effect. These studies provide the first demonstration that SFKs act to negatively regulate RA-induced gene expression and myeloid differentiation and suggest that the combination of SFK inhibition and RA treatment may be therapeutically beneficial in AML.
Mol Cancer Ther 2007 Dec
PMID:Inhibition of Src family kinases enhances retinoic acid induced gene expression and myeloid differentiation. 1806 91

Translocation (14;14)(q11;q32) is one of the recurrent chromosome aberrations in ataxia-teleangiectasia (AT) and T-cell malignancies. In patients with the t(14;14), the TCL1 and TCRalpha/delta genes were found to be involved at the molecular level. However, t(14;14)(q11;q32) is an exceedingly rare phenomenon in B-lineage acute lymphoblastic leukemia (B-ALL). To date, it has been reported in only 5 B-ALL cases. Here, we report another B-ALL case with t(14;14)(q11;q32) in a 39-year-old female. The immunophenotype of the blasts showed positivity for CD79a, CD10, CD19, and HLA-DR. Chromosome analysis of the bone marrow (BM) cells at presentation showed the karyotype 47,XX,+4,t(14;14)(q11;q32). Fluorescence in situ hybridization (FISH) demonstrated trisomy 4 and the simultaneous involvement of the IGH gene at 14q32 and the CEBPE gene at 14q11, which differs from the genes involved in T-cell leukemias. After chemotherapy, the patient achieved complete remission (CR). Later, she received allogeneic peripheral blood stem cell transplantation. After CR, the karyotype of the BM cells was normal. She was disease-free at a 6-month follow-up. We suggest that t(14;14)(q11;q32) involving the IGH and CEBPE genes in B-ALL is rare, but it is a recurrent abnormality that could identify a new subgroup of B-ALL.
Cancer Genet Cytogenet 2008 Dec
PMID:Translocation (14;14)(q11;q32) with simultaneous involvement of the IGH and CEBPE genes in B-lineage acute lymphoblastic leukemia. 1902 93

To define the molecular mechanisms that mediate hyperthermia-induced apoptosis, we performed microarray and computational gene expression analyses. U937 cells, a human myelomonocytic lymphoma cell line, were treated with hyperthermia at 42 degrees C for 90 min and cultured at 37 degrees C. Apoptotic cells ( approximately 15%) were seen 6 h after hyperthermic treatment, and elevated expression of heat shock proteins (HSPs) including Hsp27, Hsp40, and Hsp70 was detected, following the activation of heat shock factor-1. Of the 54,675 probe sets analyzed, 1334 were upregulated and 4214 were downregulated by >2.0-fold in the cells treated with hyperthermia. A non-hierarchical gene clustering algorithm, K-means clustering, demonstrated 10 gene clusters. The gene network U1 or U2 that was obtained from up-regulated genes in cluster I or IX contained HSPA1B, DNAJB1, HSPH1, and TXN or PML, LYN, and DUSP1, and were mainly associated with cellular compromise, and cellular function and maintenance or death, and cancer, respectively. In the decreased gene cluster II, the gene network D1 including CCNE1 and CEBPE was associated with the cell cycle and cellular growth and proliferation. These findings will provide a basis for understanding the detailed molecular mechanisms of apoptosis induced by hyperthermia at 42 degrees C in cells.
Cell Biol Int 2009 Dec
PMID:Gene networks involved in apoptosis induced by hyperthermia in human lymphoma U937 cells. 1973 44