UMLS:C0017638 - FACTA Search

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

S100 protein is a calcium-binding protein found in vertebrate nervous tissue. Synthesis of S100 protein in the rat glioma cell line, C6, is inhibited by the addition of anti-microtubular drugs. We have cloned a cDNA for the beta subunit of S100 protein from rat brain in a lambda gt 11 expression vector and used this cDNA to measure the amounts of S100 beta subunit mRNA in C6 cells after treatment with anti-microtubular drugs. Levels of alpha-tubulin and beta-actin mRNAs were also measured. All measurements were performed using RNA-RNA hybridization techniques at high stringency with rat mRNA-specific probes. After 24 h of treatment, the S100 beta subunit mRNA was reduced to levels of 25% by colchicine and 32% by vinblastine when compared to untreated controls. In contrast, the levels of tubulin and actin mRNAs were only slightly changed by these treatments. These studies demonstrate that disruption of the microtubular cytoskeleton causes a specific reduction in the level of S100 protein mRNA in C6 cells.
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PMID:Reduction in S100 protein beta subunit mRNA in C6 rat glioma cells following treatment with anti-microtubular drugs. 381 55

Neuroblastoma x glioma hybrid NG108-15 cells endogenously express at least three receptors which activate adenylate cyclase via the intermediacy of the stimulatory G-protein, Gs. Sustained exposure of the cells to agonists at the IP prostanoid receptor results in a substantial decrease in cellular levels of the alpha-subunit of Gs (Gs alpha) [McKenzie and Milligan (1990) J. Biol. Chem. 265, 17084-17093; Adie, Mullaney, McKenzie and Milligan (1992) Biochem J. 285, 529-536]. By contrast, equivalent treatments of the cells with agonists at either the A2 adenosine receptor or the secretin receptor have no measurable effect on cellular amounts of Gs alpha. To examine whether this is a feature specific to the IP prostanoid receptor or is related to the level of expression of the individual receptors, NG108-15 cells were transfected with a construct containing a human beta 2-adrenoceptor cDNA under the control of the beta-actin promoter. Two clones of these cells were examined in detail, beta N22, which expressed some 4000 fmol/mg of membrane protein, and clone beta N17, which expressed approx. 300 fmol/mg of membrane protein of the receptor. Exposure of beta N22 cells to the beta-adrenergic agonist isoprenaline resulted maximally in some 55% decrease in membrane-associated levels of Gs alpha, without effect on membrane levels of Gi2 alpha, Gi3 alpha, G(o) alpha or Gq alpha/G11 alpha. Dose-response curves to isoprenaline in beta N22 cells indicated that half-maximal down-regulation of Gs alpha was produced by approx. 1 nM agonist. Equivalent exposure of beta N17 cells to isoprenaline did not significantly modify levels of any of the G-protein alpha subunits, including Gs alpha. In beta N22 cells the IP prostanoid receptor was expressed at similar levels to those in wild-type NG108-15 cells, and treatment with iloprost resulted in a similar down-regulation of cellular Gs alpha levels. Iloprost was also effective in causing down-regulation of Gs alpha levels in clone beta N17. Concurrent addition of both isoprenaline and iloprost to clone beta N22 resulted in less than additive down-regulation of Gs alpha. These results demonstrate that the phenomenon of agonist-induced specific G-protein down-regulation is determined by the levels of expression of the receptor.
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PMID:Agonist regulation of cellular Gs alpha-subunit levels in neuroblastoma x glioma hybrid NG108-15 cells transfected to express different levels of the human beta 2 adrenoceptor. 751 55

Excision repair cross-complementing rodent repair deficiency genes (ERCC) are human genes implicated in nucleotide excision repair. ERCC-2 has been implicated in the repair of DNA damaged by chemotherapeutic agents, and may thus play an important role in anticancer drug resistance. ERCC-2 gene expression is low in primary tumor samples rendering it difficult to quantitate. We have developed a semiquantitative method to measure ERCC-2 gene expression utilizing reverse transcription-polymerase chain reaction (RT-PCR). Total RNA extracted from established human tumor cell lines was reverse-transcribed to obtain cDNA. Serially diluted reference ERCC-2 DNA fragment was amplified by PCR to obtain a 617-bp fragment. A standard curve was then created using densitometry readings of the 617-bp bands on agarose gel. A fixed amount of sample cDNA from each cell line was amplified at the same time and the resultant PCR product was read by densitometer. Using the standard curve, ERCC-2 gene expression in a given amount of total RNA was quantitated and normalized to beta-actin expression. There was minimal variation in three repeated experiments with PCR amplification. ERCC-2 gene expression determined by this semiquantitative PCR was also correlated to ERCC-2 quantitation by Northern blot analysis, with a significant concordance (r = 0.912, P = 0.0002). We also successfully applied this sensitive method to quantify five clinical glioma samples.
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PMID:Quantitation of ERCC-2 gene expression in human tumor cell lines by reverse transcription-polymerase chain reaction in comparison to northern blot analysis. 902 7

Cisplatin is an anticancer agent frequently used as an alternative to the nitrosoureas in brain tumor chemotherapy. We describe the use of a technique of quantitative reverse transcription-polymerase chain reaction (RT-PCR) to examine the damage induced in the glutathione S-transferase (GST)-pi gene by cisplatin and the subsequent repair of this damage in cells of the MGR3 human glioblastoma multiforme cell line. The relationship between cisplatin dose and the extent of damage in the GST-pi gene was determined over cisplatin concentrations (0-10 microM) within the clinically achievable range. Total RNA was purified from control and cisplatin-treated cells, and both the full-length GST-pi cDNA and control 200-bp beta-actin cDNA were amplified by RT-PCR. The cDNA reaction products were electrophoresed, Southern hybridized, and quantitated densitometrically. A decrease in GST-pi mRNA representing damage to the GST-pi gene was observed with increasing cisplatin concentrations, up to a maximum of 75% at 10 microM cisplatin. Repair of the GST-pi gene in cells treated with cisplatin, assessed as recovery of transcriptional activity of the gene, was shown to occur even after 48 hr following drug removal. A potent RNA polymerase II inhibitor, alpha-amanitin, was used to show that the GST-pi mRNA quantitated in this RT-PCR assay resulted from de novo RNA transcription of the GST-pi gene with little contribution from preexisting GST-pi transcripts. The results demonstrate that the GST pi gene, which is actively transcribed and often overexpressed in human glioma cells, is a target for cisplatin, but that the damage to the gene is efficiently repaired in these cells. The RT-PCR assay has the potential for use in the detection of DNA damage induced by genotoxic agents in other actively transcribed genes and for assessing the repair of gene-specific DNA lesions in cells.
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PMID:Detection of DNA damage in transcriptionally active genes by RT-PCR and assessment of repair of cisplatin-induced damage in the glutathione S-transferase-pi gene in human glioblastoma cells. 907 88

Microsatellite instability (MIN) is frequently observed in hereditary nonpolyposis colon cancer and in other sporadic cancers including gliomas. Abnormalities in at least one of five mismatch repair (MMR) genes are implicated in the development of cancers in hereditary nonpolyposis colon cancer and the associated MIN. Using a newly developed multiplex reverse transcription-PCR assay, we evaluated the expression of the five known human MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and GTBP) in human gliomas by measuring simultaneously the relative levels of the transcripts. The beta-actin gene was used as an internal control for RNA degradation and DNA contamination and as a reference for quantifying the levels of their transcripts. Of the 33 gliomas examined, 42% (14) had low expression of hMSH2 (at least 4-5-fold lower than normal mean), 21% (7) had low expression of hMLH1, and 18% (6) had low expression of hPMS1 compared with the expression in the lymphocytes from 13 normal individuals. Furthermore, six of the 33 (18%) tumor samples had decreased expression of more than one MMR gene. Two of these six patients with multiple gene abnormalities had second primary cancers, and an additional patient had multifocal gliomas. Further molecular analysis of available DNA samples indicated that one of five of those tumors with aberrant expression of MMR genes had MIN, as compared with none of five tumors with normal expression. These data suggest that reduced expression of MMR genes is frequent in human gliomas and that aberrant expression of more than one MMR gene may be associated with increased risk of second primary malignancies in glioma patients.
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PMID:Reduced expression of mismatch repair genes measured by multiplex reverse transcription-polymerase chain reaction in human gliomas. 913 6

A novel compound, TDN-345, not bearing catechol moiety, induced NGF synthesis/secretion in C6-10A glioma cells. Both intracellular and extracellular nerve growth factor (NGF) protein levels increased within 3 h and reached a maximum around 12 h after the addition of TDN-345. The induction of NGF synthesis/secretion by TDN-345 occurred in a concentration-dependent manner, beginning with about 0.1 microM and reaching a maximum at 10 microM. The ED50 was 0.88 microM. The induction was accompanied by an increase in NGF mRNA but not beta-actin mRNA. In a time-course study, the NGF mRNA level was found to reach a maximum 2-3 h after the addition of TDN-345 and then to return to control levels. The induction occurred dose-dependently. The catecholaminergic compound epinephrine, which induces NGF synthesis/secretion, increased the intracellular cyclic AMP content by more than 1000-times at 10 microM. In contrast, TDN-345 did not cause such a prominent increase in cAMP even at 100 microM. These results indicate that TDN-345 induces NGF synthesis/secretion by increasing NGF mRNA expression, and the action of TDN-345 clearly differs from that of epinephrine, as it does not seem to involve cAMP as a second messenger. The results of the present study suggest the existence of a signal transduction pathway for NGF synthesis/secretion which is not mediated by cAMP.
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PMID:The novel compound TDN-345 induces synthesis/secretion of nerve growth factor in C6-10A glioma cells. 945 96

Many cases of early-onset familial Alzheimer's disease have been linked to mutations within two genes encoding the proteins presenilin-1 and presenilin-2. The presenilins are 48-56-kDa proteins that can be proteolytically cleaved to generate an N-terminal fragment (approximately 25-35 kDa) and a C-terminal fragment (approximately 17-20 kDa). The N- and C-terminal fragments of presenilin-1, but not full-length presenilin-1, were readily detected in both human and mouse cerebral cortex and in neuronal and glioma cell lines. In contrast, presenilin-2 was detected almost exclusively in cerebral cortex as the full-length molecule with a molecular mass of 56 kDa. The association of the presenilins with detergent-insoluble, low-density membrane microdomains, following the isolation of these structures from cerebral cortex by solubilization in Triton X-100 and subsequent sucrose density gradient centrifugation, was also examined. A minor fraction (10%) of both the N- and C-terminal fragments of presenilin-1 was associated with the detergent-insoluble, low-density membrane microdomains, whereas a considerably larger proportion of full-length presenilin-2 was present in the same membrane microdomains. In addition, a significant proportion of full-length presenilin-2 was present in a high-density, detergent-insoluble cytoskeletal pellet enriched in beta-actin. The presence of the presenilins in detergent-insoluble, low-density membrane microdomains indicates a possible role for these specialized regions of the membrane in the lateral separation of Alzheimer's disease-associated proteins within the lipid bilayer and/or in the distinct functions of these proteins.
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PMID:Characterization of detergent-insoluble complexes containing the familial Alzheimer's disease-associated presenilins. 1009 59

Calpain, a Ca2+-activated cysteine protease, has been implicated in apoptosis of immune cells. Since central nervous system (CNS) is abundant in calpain, the possible involvement of calpain in apoptosis of CNS cells needs to be investigated. We studied calpain expression in rat C6 glioma cells exposed to reactive hydroxyl radical (.OH) [formed via the Fenton reaction (Fe2++H2O2+H+-->Fe3++H2O+.OH)], interferon-gamma (IFN-gamma), and calcium ionophore (A23187). Cell death, cell cycle, calpain expression, and calpain activity were examined. Diverse stimuli induced apoptosis in C6 cells morphologically (chromatin condensation as detected by light microscopy) and biochemically [DNA fragmentation as detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay]. Oxidative stress arrested a population of C6 cells at the G2/M phase of cell cycle. The levels of mRNA expression of six genes were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR). Diverse stimuli did not alter beta-actin (internal control) expression, but increased calpain expression, and the upregulated bax (pro-apoptotic)/bcl-2 (anti-apoptotic) ratio. There was no significant increase in expression of calpastatin (endogenous calpain inhibitor). Western blot analysis showed an increase in calpain content and degradation of myelin-associated glycoprotein (MAG), a calpain substrate. Pretreatment of C6 cells with calpeptin (a cell-permeable calpain inhibitor) blocked calpain overexpression, MAG degradation, and DNA fragmentation. We conclude that calpain overexpression due to.OH stress, IFN-gamma stimulation, or Ca2+ influx is involved in C6 cell death, which is attenuated by a calpain-specific inhibitor.
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PMID:Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells. 1035 May 26

Caspase-8 is a member of the family of caspases, which are involved in the execution of apoptosis. To investigate whether caspase-8 can be used for gene therapy of gliomas, we transduced A-172 and U251 glioma cells with the caspase-8 gene via an adenoviral vector (Adv) controlled by the chicken beta-actin (CA) promoter (Advcaspase-8), and found that a similar level of caspase-8 protein induced A-172 cells to undergo necrotic cell death and U251 cells to undergo apoptotic cell death. Neither Bcl-XL nor Bcl-2, which play important roles in antiapoptotic mechanisms in gliomas, protected glioma cells from apoptosis induced by overexpression of caspase-8. Injection of Adv-caspase-8 suppressed the in vivo growth of U251 xenografts, in which apoptotic cell death remarkably increased as revealed by TUNEL analysis. Finally, we assessed whether gene therapy with a tissue-specific promoter, the myelin basic protein (MBP) promoter, is applicable to gliomas. Adv for caspase-8 controlled by the MBP promoter induced drastic apoptosis in U251 and U-373MG glioma cells, whereas it did not induce apoptosis in human endothelial cells, fibroblasts, and nerve growth factor-treated PC12 cells. These results indicate that Adv for caspase-8 effectively induced cell death in gliomas, and that this approach may be a useful modality for gene therapy of gliomas.
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PMID:Adenovirus-mediated transfer of caspase-8 augments cell death in gliomas: implication for gene therapy. 1083 15

The effect of cellular density on insulin-like growth factor I (IGF-I) gene expression was characterized in several tumor-derived cell lines. IGF-I messenger RNA (mRNA) transcripts increased more than 200-fold when C6 glioma cells grew to postconfluence. IGF-I receptor and beta-actin mRNAs were induced by 6- and 2-fold, respectively, as a function of confluence. IGF-I mRNA transcripts in GH3 and SK-N-MC cells increased about 4- to 5-fold in confluent cultures compared with sparse cultures. In OVCAR-3 cells, the IGF-I mRNA level remained constant as the cell density increased. Transient transfection experiments were performed with IGF-I exon 1 promoter/luciferase fusion constructs in C6 cells. The luciferase activity of a construct containing exon 1 sequence between +75 and +282 (the most 5' transcription initiation site was designated +1) was stimulated by 2.5-fold in dense cultures compared with that in sparse cultures of C6 cells. Luciferase activities of other constructs containing at least 282 bp of exon 1 sequence were also stimulated about 2- to 4-fold by cell density. However, 3' deletion to +192 led to loss of the cell density stimulatory effect. In contrast, luciferase activities of IGF-I promoter constructs were not altered by cell density in SK-N-MC cells. When the conditioned medium of low density C6 cultures was exchanged with that of high density cultures, the IGF-I mRNA level remained the same. In summary, cell density has a cell type- and gene type-specific effect on IGF-I gene expression. A cell density response element(s) may be located between +192 and +282 of the exon 1 promoter region in C6 cells.
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PMID:Cell density influences insulin-like growth factor I gene expression in a cell type-specific manner. 1087 49

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