Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate which cytokine receptors may be expressed by human glioblastoma and normal astrocytic cells, the presence of messenger ribonucleic acid (RNA) for a number of cytokine receptors was examined in 16 glioblastoma cell lines and adult and fetal astrocytes. A complementary deoxyribonucleic acid copy of total RNA was synthesized and amplified with specific primers using the polymerase chain reaction method. The receptors studied were interleukin (IL)-1 receptor type I (IL-1RI) and type II (IL-1RII), p75 and p55 tumor necrosis factor (TNF) receptors (p75TNFR and p55TNFR), interferon (IFN)-alpha/beta and -gamma receptors (IFN-alpha/beta R and IFN-gamma R), granulocyte-macrophage (GM) colony-stimulating factors receptor alpha subunit (GM-CSFR), G-CSF receptor (G-CSFR), M-CSF receptor (c-fms, M-CSFR), stem cell factor receptor (c-kit, SCFR), IL-6 receptor (IL-6R), and IL-8 receptor (IL-8R). Transcripts for IL-1RI, p55TNFR, IFN-alpha/beta R, and IFN-gamma R were present in all cell lines. The presence of IL-1RII, p75TNFR, GM-CSFR, M-CSFR, SCFR, IL-6R, and IL-8R was identified in 13, eight, seven, eight, 14, three, and one cell lines, respectively. Normal astrocytes were positive for IL-1RI, p75TNFR, p55TNFR, IFN-alpha/beta R, IFN-gamma R, M-CSFR, and SCFR, showing a similarity to glioblastoma cells. Expression of IL-1RII was observed in adult astrocytes but not in fetal astrocytes. Furthermore, gene expression was assessed in normal brain tissue and 11 glioblastoma tissue specimens. The normal brain tissue expressed IL-1RI, IL-1RII, IFN-alpha/beta R, M-CSFR, and SCFR. Of the 11 glioblastoma tissue specimens, IL-1RI was positive in 11, IL-1RII in 10, p75TNFR in nine, p55TNFR in nine, IFN-alpha/beta R in 10, IFN-gamma R in 10, GM-CSFR in two, G-CSFR in three, IL-8R in eight, and M-CSFR and SCFR in 11. These expressions were consistent with those in the cell lines, except for IL-8R. It is concluded that glioblastoma cells and normal astrocytes express a similar set of cytokine receptor genes in vitro and in vivo. Possible autocrine loops are suggested for IL-1 alpha/IL-1RI, TNF-alpha/p55TNFR, IFN-beta/IFN-alpha/beta R, M-CSF/M-CSFR, and SCF/SCFR in glioblastomas.
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PMID:Analysis of cytokine receptor messenger RNA expression in human glioblastoma cells and normal astrocytes by reverse-transcription polymerase chain reaction. 751 61

Eighty six of 430 acute myeloblastic leukemia (AML) patients (20.0%) and forty of 173 acute lymphoblastic leukemia (ALL) patients (23.1%) had CD7 on their leukemia cells. CD7(+) AML occurred at a younger age than CD7(-) AML, and is more frequent in males. Hepatomegaly and central nervous system involvement were also more frequent in CD7(+) AML than in CD7(-) AML. The age of onset of CD7(+) ALL is also younger than that of CD7(-) ALL. Phenotypically, CD(+) AML expressed CD34, HLA-DR, and TdT more frequently than CD7(-) AML while CD7(+) ALL expressed CD13/33 more often than CD7(-) ALL cells responded most significantly to interleukin 3 (IL-3), whereas most CD7(-) AML cells responded more significantly to granulocyte macrophage-colony stimulating factor (GM-CSF) and/or granulocyte (G)-CSF than to IL-3. CD7(+)sCD3(-)CD4(-)CD8(-) ALL expressed G-CSF receptor and c-kit mRNA more frequently, which is not usual in other types of ALL. P-glycoprotein (P-gp)/multi-drug resistance gene (MDR1), thought to be expressed in hematopoietic stem cells, is expressed in CD7(+) AML and CD7(+)sCD3(-) CD4(-)CD8(-) ALL significantly more often than in CD7(-) acute leukemias and the CR rate and overall survival of CD7(+)AML was worse than CD7(-) AML. These data, collectively, suggest the close association of CD7(+) AML and CD7(+)sCD3(-)CD4(-)CD8(-) ALL, not only the common expression of CD7 itself but also because their phenotypical immaturity, cytokine receptor expression, P-gp/MDR1 expression and clinical manifestations including the frequent occurrence in males and the poor prognosis. We propose that CD7(+) acute leukemia is an hematopoietic stem cell leukemia which may be separate entity.
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PMID:Biological characteristics of CD7(+) acute leukemia. 872 5

The kinetics of colony formation by granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) were monitored using clone-mapping experiments. Compared with normal resting bone marrow (BM), where the ratio of Day 7:Day 14 granulocyte-macrophage colony-forming cells (GM-CFCs) was 1:0.76-1.9, PB was found to be relatively deficient in progenitor cells with the capacity to form colonies by Day 7 (median ratio Day 7:Day 14 1:21). The most mature Day 7 GM-CFCs, those dispersing or extinguishing before Day 14, were almost absent in PB (< 1% of all GM-CFCs) but comprised 77% of Day 7 GM-CFCs and 32% of all GM-CFCs in BM. The expression patterns of high affinity receptors for G-CSF, GM-CSF, stem cell factor (SCF), and the ligand for flk-2 on CD38hi and CD38-/dim PB CD34+ cells were determined by binding of 125I-labeled ligand and autoradiography. G-CSF receptor (G-CSFR) expression was detected on approximately 25% of CD38-/dim cells (estimated mean 105 receptors per positive cell) and was higher in CD38hi cells (approximately 50% positive, with a mean of 227 receptors per cell). GM-CSFR expression was low (approximately 25% of cells positive, mean of 120 receptor per cell) and did not vary with CD38 expression. c-kit (SCFR) and flk-2 were expressed by > or = 90% and > or = 80% of CD34+ cells, respectively. SCF binding per cell was greater in the CD38hi population, while flk-2 expression did not vary with CD38 expression. These results confirm the heterogeneity of receptor expression by progenitor cells and imply differential regulation of receptor expression during maturation.
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PMID:G-CSF-mobilized peripheral blood progenitor cells: in vitro growth pattern and hematopoietic growth factor receptor profile. 913 Oct 4

Hematopoietic stem cells (HSCs) generate all known hematopoietic lineages and are capable of self-renewal. Upon aging, myeloid-biased HSCs are maintained, whereas lymphoid-biased HSCs are lost. GADD34 protein is expressed in myeloid-lineage cells and has been cloned from them. However, the function of GADD34 in the myeloid lineage has not yet been elucidated. Here, we show that early age-dependent deviation to the myeloid lineage occurs in GADD34-deficient mice. Early increases of GR-1(int)CD11b(+) and GR-1(high)CD11b(+) neutrophils were observed in the spleen, bone marrow (BM) and blood of GADD34-deficient mice. We found that BM Lin(-) c-Kit(+) Sca1(+) and Lin(-) c-Kit(+) Sca1(-)cells expressed GADD34 protein without stimulation and increased GADD34 expression following intravenous injection of Staphylococcus aureus (S.aureus). These cell populations were high in GADD34-deficient BM and were increased by the injection of S. aureus. Because of the increase in granulocyte colony-stimulating factor (G-CSF) induced by S. aureus injection, we examined the signaling pathway from the G-CSF receptor (G-CSFR). We found that phosphorylation of signal transducer and activator of transcription factor 3 was highly increased in GADD34-deficient Lin(-) BM cells by the stimulation of G-CSF. These results indicate that GADD34 binds to Lyn and inhibit G-CSFR signaling. We show here that GADD34 works to inhibit the proliferation and differentiation of HSCs or myeloid precursor cells and maintains homeostatic differentiation of neutrophil-lineage cells to avoid early immunological senescence.
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PMID:Loss of GADD34 induces early age-dependent deviation to the myeloid lineage. 2441 16