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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ciliary neurotrophic factor (CNTF) has been shown to modulate the in vitro and in vivo survival, proliferation and differentiation of many neuronal cell types. Evidence indicates that it produces most if not all these effects by binding to a receptor subunit referred to as the CNTF receptor alpha component (CNTFR alpha). We cloned a cDNA encoding part of the rat CNTFR alpha and used it in Northern analyses to study CNTFR alpha mRNA expression. Examination of various tissues of embryonic day 18 and postnatal day 14 rats indicated that CNTFR alpha mRNA is primarily but not exclusively expressed in brain at these stages of development. Further studies revealed that the CNTFR alpha transcripts are present throughout brain development from embryonic day 12 to adulthood and display a widespread distribution in the adult brain. A survey of rodent cell lines detected highest CNTFR alpha mRNA concentrations in neuronal lines and a low concentration in a Schwann cell derived line. CNTFR alpha mRNA was not detected in fibroblast lines and a glioma line. Finally, nerve growth factor treatment decreased CNTFR alpha mRNA levels in PC12 cells. This result demonstrates that signal transduction processes activated by a neurotrophin can influence CNTF activated signal transduction processes. Such cross-talk may play an important in vivo role in the development and maintenance of the many neuronal cell types that are responsive to both neurotrophins and CNTF.
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PMID:CNTF receptor alpha mRNA expression in rodent cell lines and developing rat. 780 24

Cells that lack the high affinity receptor component (trkA) for nerve growth factor (NGF) are unresponsive to NGF. We investigated whether C6-2B cells, a rat glioma derived cell line, express trkA and, as a consequence, are responsive to NGF. In these cells, NGF (100 ng/ml) failed to induce the mRNA encoding for c-fos protooncogene and the low affinity NGF receptor p75NGFR, two NGF-responsive genes. In contrast, both mRNAs were induced in PC12 cells by NGF. Using a RNase protection assay with a cRNA probe for rat trkA, the expected trkA RNA protected fragment was detected in PC12 but not in C6-2B glioma cells, indicating that C6-2B cells either do not express the gene or express it only in low amounts. Cross-linking of 125I-labeled NGF to PC12 cells identified two major bands with an apparent molecular weight of 158 kDa and 100 kDa corresponding to trkA and p75NGFR, respectively. In contrast, only the 100 kDa band could be detected in C6-2B cells by cross-linking analysis. In C6-2B cells stably transfected with the rat trkA cDNA, NGF increased c-fos mRNA, induced tyrosine phosphorylation of gp140trk, and SNT (suc-associated neurotrophic factor-induced tyrosine-phosphorylated target), and caused morphological changes within 72 h. All of these effects of NGF were blocked by the protein kinase inhibitor K-252a suggesting that NGF signal transduction was restored by trkA expression. Most important, in C6trk+ cells, NGF was a weaker (2-fold) inducer of [3H]thymidine incorporation when compared to bFGF (5-fold), suggesting that expression of trkA fails to confer to NGF a strong mitogenic effect. Our findings indicate that C6-2B glioma cells do not possess high affinity NGF receptor and thus are unresponsive to NGF and that expression of trkA in neuroectoderm derived cells elicits some of the NGF responses characteristic of neuronal cells.
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PMID:Induction of nerve growth factor responsiveness in C6-2B glioma cells by expression of trkA proto-oncogene. 786 85

Retinoic acid (RA) and nerve growth factor (NGF) are both differentiation factors for central nervous system tumours. Mouse-derived NGF inhibits proliferation of C6 glioma cells in vivo in the absence of serum. Retinoic acid inhibits in vivo growth of C6 gliomas in the subcutaneous tissue of rats. This study evaluated the response of C6 cells implanted in the rat cortex to NGF, RA, or a combination of the two in 89 rats. Tumour size, cellular density and morphology were analysed using light microscopy. Treatment with RA alone resulted in tumour volumes that were 38% of control and 48% of NGF-treated groups. There was no significant difference in the tumour volumes or in cell morphology in C6 cells treated with NGF alone compared to controls. Tumours treated with a combination of RA and NGF were larger however, than tumours treated with RA alone. This suggests that despite the growth inhibitory effects of NGF in vitro, NGF acts to prevent the growth inhibitory effect of RA in vivo.
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PMID:Trans retinoic acid inhibits in vivo tumour growth of C6 glioma in rats: effect negatively influenced by nerve growth factor. 793 86

The effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3) on nerve growth factor (NGF) synthesis was investigated in primary cultures of astrocytes prepared from brain of neonatal rats. 1,25-(OH)2 D3 elicited a dose-dependent increase of NGF mRNA with a maximal effect at 10(-7) M, which persisted for at least 48 h. Northern blot analysis revealed an expression of the vitamin D3 receptor (VDR) gene in primary glial cells. Treatment of cells with 1,25-(OH)2 D3 led to an increase in the VDR mRNA levels. Similar results were obtained in C6 glioma cells. Exposure of primary glial cells to 10(-8) M 1,25-(OH)2 D3 caused only a 2-fold increase of the levels of cell-secreted NGF after 3 days of treatment. However, a 5-fold increase was observed three days after a second addition of vitamin D3. Likewise, a pretreatment with lower doses of hormone such as 10(-10) M or 10(-9) M enhanced the responsiveness of the cells to a 24 h treatment with 10(-8) M hormone. It appears, therefore, that the duration of the treatment influences the level of synthesis of NGF, possibly as a consequence of the increase of the VDR gene expression. The specificity of 1,25-(OH)2 D3 is supported by the fact that a concentration of 10(-7) M of an another vitamin D3 metabolite, 24,25-(OH)2 D3, had no effect on NGF synthesis. Several lines of evidence indicate that astrocytes constitute the major cell type responsive to 1,25-(OH)2 D3 in primary cultures of glial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells. 796 79

The role of the low-affinity neurotrophin receptor (p75NTR) in signal transduction is undefined. Nerve growth factor can activate the sphingomyelin cycle, generating the putative-lipid second messenger ceramide. In T9 glioma cells, addition of a cell-permeable ceramide analog mimicked the effects of nerve growth factor on cell growth inhibition and process formation. This signaling pathway appears to be mediated by p75NTR in T9 cells and NIH 3T3 cells overexpressing p75NTR. Expression of an epidermal growth factor receptor-p75NTR chimera in T9 cells imparted to epidermal growth factor the ability to activate the sphingomyelin cycle. These data demonstrate that p75NTR is capable of signaling independently of the trk neurotrophin receptor (p140trk) and that ceramide may be a mediator in neurotrophin biology.
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PMID:Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. 807 74

The glioma cell line C6 was used to study the expression and growth-dependent regulation of the nerve growth factor (NGF) tyrosine kinase receptor gp140trk, which is the mature protein product of the trk proto-oncogene. Chemical cross-linking of 125I-NGF to C6 cells, followed by immunoprecipitation with polyclonal anti-NGF antibodies and separation by polyacrylamide gel electrophoresis, revealed the presence of 90-95 and 150 kDa species. Immunocytochemical staining of C6 cells with antibodies directed against either the low-affinity NGF receptor gp75NGFR or trk proto-oncogene products demonstrated a heterogeneous cellular distribution of both antigens. Brief treatment of C6 cells with NGF led to the tyrosine phosphorylation of 80, 110 and 140 kDa protein species, as detected on anti-phosphotyrosine Western blots. Similar molecular weight species were found with anti-Trk antibodies in the NGF-treated cells. Intracellular localization of Trk-like immunoreactivity in C6 cells released from a growth-arrested state indicated an initial immunostaining of the nuclear periphery, progressing to cytoplasmic vesicles and finally to the plasma membrane. These observations at the light microscopic level were confirmed using immunoelectron microscopy with the same anti-Trk antibodies, and showed clearly the trafficking of Trk-like immunostained particles from the endoplasmic reticulum to the plasmalemma. The cellular localization of trk gene products also appeared to depend on their glycosylation state. Such growth-dependent expression of NGF receptors on glial cells may be important in controlling autocrine regulatory processes of glia to NGF, which these cells produce.
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PMID:Characterization and growth-dependent regulation of the nerve growth factor receptor gp140trk in rat C6 glioma cells. 809 70

The biological responsiveness of neural cells to nerve growth factor (NGF) appears to require expression and ligand binding to both the low-affinity NGF receptor (LNGFR) and the proto-oncogene product trk, the latter being a receptor tyrosine kinase. Immunolocalization of the LNGFR and the high-affinity component of the NGF receptor, trk (HNGFR) was studied by electron microscopic morphometric analysis on cultured PC12 pheochromocytoma cells, C6 glioma cells and neonatal rat dorsal root ganglia neurons using a double immunogold labeling technique. Two receptor-specific antibodies, anti-LNGFR monoclonal antibody 192-IgG and a polyclonal antibody against the 14 carboxy-terminal amino acids of the Trk protein, were utilized in conjunction with immunoglobulin conjugated to colloidal gold particles of different sizes. All cells treated with NGF (50 ng/ml) displayed significant colocalization of LNGFR/HNGFR-like immunoreactivity. Gold particles associated with LNGFR (LNGFR-like immunoreactivity) were frequently seen near 2 or 3 (or more) particles delineating the HNGFR on all cell surfaces. Positive Trk-like immunoreactivity (HNGFR) thus seems to localize in close proximity to LNGFRs in at least these cell types.
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PMID:Colocalization of low- and high-affinity NGF receptors on PC12 cells, C6 glioma cells and dorsal root ganglion neurons. 822 16

The characteristics of KCl-stimulated 45Ca uptake by neuroblastoma X glioma hybrid NG108-15 cells induced to differentiate with dibutyryl cAMP (Bt2cAMP) and of PC12h pheochromocytoma cells induced to differentiate with nerve growth factor (NGF) were studied. The extent and rate of KCl-stimulated 45Ca uptake by differentiated NG108-15 cells induced with Bt2cAMP were significantly higher than those of the undifferentiated cells. However, differentiation of PC12h cells induced with NGF did not enhance their extent or rate of KCl-stimulated 45Ca uptake. The effects of Ca agonist and antagonists indicated that the characteristics of KCl-stimulated 45Ca uptake by Bt2cAMP-treated NG108-15 cells and NGF-treated PC12h cells mainly reflected those of peripheral L-type voltage-sensitive calcium channels activated by high KCl. These results suggest that differentiated neural cells did not all show an enhanced capacity for KCl-stimulated 45Ca uptake, although the characteristic patterns of differentiation (extension of neurite-like processes, etc.) and that of effect by Ca agonist or antagonists on NG108-15 cells and PC12h cells were similar.
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PMID:Characteristics of 45Ca uptake stimulated by high KCl of differentiated and undifferentiated NG108-15 and PC12h cells. 838 38

The low-affinity nerve growth factor (NGF) receptor (LNGFR) binds the neurotrophins NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) with similar affinities. Here we report on the ability of NT-3 to regulate the expression of the LNGFR in C6 glioma cells. LNGFR-like immunoreactivity (LNGFR-IR) was examined in C6 cells treated for 16 h with NT-3 and exposed to the antibody 192-IgG followed by immunoglobulins conjugated with colloidal gold by means of ultrastructural morphometric analysis. Untreated C6 cells exhibited some positive LNGFR-IR, while C6 cells treated with NT-3 displayed significantly increased (2.3 fold) LNGFR-IR. The increase in LNGFR protein was accompanied by a greater quantity of LNGFR mRNA in NT-3-treated cells. Thus, LNGFR can be upregulated by the structurally related neurotrophin NT-3.
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PMID:Neurotrophin-3 upregulates NGF receptors in a central nervous system glial cell line. 845 34

Regulation of the cytosolic free Ca2+ concentration by nerve growth factor was investigated in C6-2B glioma cells newly expressing the high affinity nerve growth factor receptor trkA, using Fura-2 fluorescence ratio imaging. In these cells, nerve growth factor (50 ng/ml) evoked a novel approximately 3-fold increase in cytosolic free Ca2+ concentration, while no measurable Ca2+ response was observed in wild type or mock-transfected cells lacking a functional trkA receptor. K-252a, a tyrosine kinase inhibitor which prevents nerve growth factor-mediated responses in C6-2B cells expressing trkA, also blocked the rise in cytosolic free Ca2+ concentration by nerve growth factor. Moreover, basic fibroblast growth factor, which in these cells elicits biochemical changes similar to nerve growth factor, failed to affect cytosolic free Ca2+ concentration, further supporting the specificity of nerve growth factor/trkA receptor in mediating a Ca2+ response. While insensitive to chelation of extracellular Ca2+, the response was abolished following depletion of Ca2+ stores or blockade of intracellular Ca2+ release, providing strong evidence that intracellular Ca2+ is the main source for nerve growth factor-evoked cytosolic free Ca2+ concentration increase. Nerve growth factor increased the cytosolic free Ca2+ concentration also in NIH3T3 cells overexpressing trkA but devoid of p75 nerve growth factor receptor. Our data suggest that trkA but not p75 is required for nerve growth factor-evoked Ca2+ signaling.
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PMID:TrkA mediates the nerve growth factor-induced intracellular calcium accumulation. 862 95


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