Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigate the linkage between the transcriptional factor, c-fos, and expression of proenkephalin in rat C6 glioma cells. C6 cells contained abundant levels of c-fos mRNA. Treatment of cells with dexamethasone resulted in a 10-fold decline in c-fos transcripts and a small increase in proenkephalin mRNA. Combined exposure to dexamethasone and isoproterenol also induced a decrease in c-fos mRNA while proenkephalin mRNA increased 8-fold. Treatment of the C6 cells with phorbol 12-myristate 13-acetate caused a 13-fold increase in c-fos expression 0.5 h after administration and a decrease in proenkephalin mRNA. These data indicate that c-fos and proenkephalin mRNA are not regulated in a sequential, parallel manner, that newly synthesized c-fos is not the determining factor controlling proenkephalin gene regulation, and that c-fos expression is under negative control by glucocorticoids.
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PMID:Glucocorticoid-mediated down regulation of c-fos mRNA in C6 glioma cells: lack of correlation with proenkephalin mRNA. 131

The regulation by intrinsic factors of responses to stress of two small stress proteins, hsp27 and alpha B crystallin, was examined in C6 rat glioma cells. Levels of hsp27 and alpha B crystallin were low in C6 glioma cells in confluent cultures. However, levels of the two proteins increased after exposure of cells to heat (42 degrees C for 30 min) or arsenite (50 microM for 1 h) stress. When cells were exposed to arsenite or hear in the presence of indomethacin (50 microM), an inhibitor of cyclooxygenase, or in the presence of nordihydroguaiaretic acid (NDGA; 50 microM), an inhibitor of lipoxygenase, induction of hsp27 and alpha B crystallin was markedly stimulated as detected by specific immunoassays, Western blot analysis, and Northern blot analysis. The presence of melittin (1 microM), an activator of phospholipase A2, during the stress period also stimulated the induction of the two proteins. The expression of hsp70 to each stress was also enhanced in the presence of indomethacin, NDGA, or melittin. The gel mobility shift assay revealed that these chemicals prolonged the arsenite-induced activation of heat shock element (HSE)-binding activity of heat shock transcriptional factor (HSF) in cells. Induction of hsp27 and alpha B crystallin in adrenal glands of heat-stressed (42 degrees C for 15 min) rats was also enhanced by prior injection of aspirin, another inhibitor of cyclooxygenase. These results indicate that the responses to stress of hsp27 and alpha B crystallin, as well as the response of hsp70, are coupled with the metabolic activity of the arachidonic acid cascade and the mechanism for regulation of stress responses observed in C6 cells is operative in tissues and organs in vivo.
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PMID:Enhancement of stress-induced synthesis of hsp27 and alpha B crystallin by modulators of the arachidonic acid cascade. 859 93

In rat type I astrocytes and C6 glioma cells, sphingosine 1-phosphate (S1P) clearly induced the expression of fibroblast growth factor-2 (FGF-2) mRNA to an extent comparable to that achieved by platelet-derived growth factor (PDGF) and endothelin. In C6 cells, Western blotting showed that S1P also induced expression of early growth response-1 (Egr-1), one of the immediate early gene products and an essential transcriptional factor for FGF-2 expression. On the other hand, sphingosine, a substrate for sphingosine kinase which forms intracellular S1P, was a very weak activator for the expression of either FGF-2 or Egr-1. The S1P-induced Egr-1 expression was partially inhibited by treatment of the cells with either calphostin C, an inhibitor of protein kinase C (PKC), or pertussis toxin (PTX), and completely inhibited by the combination of these agents. Essentially, the same inhibitory pattern by these agents has been observed for S1P-induced extracellular signal-regulated kinase (ERK) activation. The S1P-induced expression of Egr-1 was also completely inhibited in association with complete inhibition of ERK by PD 98059, an ERK kinase inhibitor. Thus, the S1P-induced activation of the Egr-1/FGF-2 system may be mediated through ERK activation, which may involve at least two signaling pathways, i.e., a PTX-sensitive G-protein-dependent pathway and a PKC-dependent pathway.
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PMID:Sphingosine 1-phosphate induces expression of early growth response-1 and fibroblast growth factor-2 through mechanism involving extracellular signal-regulated kinase in astroglial cells. 1064 Jun 89

The interleukin 13 alpha 2 receptor (IL-13Ra2) has been shown to be expressed in most malignant glioblastoma cells. Recent studies suggest that IL-13Ra2 serves as a dominant negative inhibitor or a decoy receptor for IL-13. To investigate the transcriptional regulation of this receptor, we cloned and characterized the promoter for the human IL-13Ra2 gene. Our results demonstrate that this promoter contains three TATA boxes and one CCAAT site. Several putative transcriptional factor binding sites for nuclear factor of activated T cells 1, AP1 (c-JUN and c-FOS), AP2, GABP, OCT1, GATA3, PRE, and C-ETS1 were predicted in the promoter region. Using the secreted alkaline phosphate reporter gene assay, we investigated the functional activity of the human IL-13Ra2 promoter by transient transfection in glioma cell lines U118, U87, and T98, which differ in their expression of the human IL-13Ra2 protein. The different secreted alkaline phosphate activities among these 3 cell lines suggest that the expression of human IL-13Ra2 is regulated at the transcriptional level. Methylation analysis showed that expression of IL-13Ra2 may not be the result of methylation of the CpG dinucleotides in the promoter region of the gene. Deletion analysis identified a 64 base pair (bp) region that is necessary for human IL-13Ra2 promoter activity. This 64-bp sequence contains cis-elements for AP1, nuclear factor of activated T cells, and AP2. The possible role of AP1 in the regulation of human IL-13Ra2 promoter activity was suggested by in vitro mutagenesis and c-JUN N-terminal kinase inhibition analysis.
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PMID:Molecular cloning and identification of the human interleukin 13 alpha 2 receptor (IL-13Ra2) promoter. 1281 24

To identify tumor antigens for glioma, a human testis cDNA library was screened by serological identification of antigens by recombinant expression cloning with sera from glioma patients. In this screening, the most frequently isolated antigen was SOX6, an Sry-related high-mobility group (HMG) box-containing gene. SOX6 is a transcriptional factor that is specifically expressed in the developing central nervous system and in the early stages of chondrogenesis in mouse embryos. IgG antibodies against SOX6 were detected in sera from 12 of 36 glioma patients (33.3%), 0 of 14 patients with other brain disease (0%), and one of 54 other cancer patients (1.9%). In sera from 37 healthy individuals, no IgG responses against SOX6 were detected, except in an elderly female. Furthermore, Western blot and ELISA analyses with sera from glioma patients revealed that the DNA-binding domain, the HMG box of SOX6, might be a dominant epitope of IgGs against SOX6. RT-PCR and Northern blot analysis revealed that the SOX6 gene was more highly expressed in glioma tissues than in normal adult tissues, except testis. Western blot analysis with an anti-SOX6 antibody demonstrated that the SOX6 protein was expressed in glioma tissues, but not in normal adult brain tissue. Immunohistochemical analysis with the anti-SOX6 antibody showed that all the glioma tissues analysed expressed SOX6 in tumor cells, but only a few SOX6-positive cells were detected in non-neoplastic tissues from the cerebral cortex. In summary, these results indicate that the developmentally regulated transcription factor SOX6 is aberrantly expressed in glioma and specifically recognized by IgGs from glioma patients' sera.
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PMID:Identification of a human glioma antigen, SOX6, recognized by patients' sera. 1469 56

Heat shock factor binding protein 1(HSBP1) is a nuclear-localized, novel, conserved, low molecular weight (< 100 residues) transcriptional factor, which may repress the activity of the heat shock factor 1 (HSF1) by binding HSF1 active trimerization domain. HSBP1 gene have been cloned in human and mouse, but not reported in rat. In this paper, a pair of consensus degenerate primers were designed based on N-terminal and C-terminal conservative amino acid sequence. Using RT-PCR method, hsbp1 gene fragment was amplified and cloned from total RNA extracted from rat C6 glioma cells. Then the EST was probed to isolate the rat full-length hsbp1 cDNA by in situ hybridization from a rat C6 glioma cells cDNA library. The full-length hsbp1 was deposited in GenBank (accession No. AY522937). It was blasted in RGD (rat genome database) and was localized in 19q12 and composed of four extrons and three introns. The distance between the first extron and the fourth extron was 5829bp. Then its Uinigene was searched, results showed HSBP1 existed widely in all kinds of organs and tissues, the data suggested that it may play a important roles in physiological activity. In addition, the sequence similarity and phylogenetic relationship were compared with DNAman tool. The result showed the relationship is consistent between the similarity of amino acid sequence and phylogenetic evolution from morphological of those species which were nearly in evolution.
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PMID:[Cloning and analysis of rat heat shock factor binding protein 1 cDNA]. 1564 79

By screening a human testis cDNA library with glioma patients' sera, we isolated a transcriptional factor, SOX6. Here, we analyzed SOX6 expression in gliomas having a range of malignancy grades using immunostaining. Murine Sox6 is a transcriptional factor that is specifically expressed in the developing central nervous system and in the early stages of chondrogenesis in mouse embryos. The reverse transcription-polymerase chain reaction (RT-PCR) revealed that the SOX6 gene was more highly expressed in glioma tissues and fetal brain than in normal adult brain and other cancer cells, except melanoma cells. Immunohistochemical analysis with the anti-SOX6 antibody showed that all the glioma tissues analyzed (14 glioblastomas, 14 anaplastic astrocytomas, 3 anaplastic oligoastrocytomas, 5 diffuse astrocytomas, 1 oligodendroglioma, and 1 pilocytic astrocytoma) expressed SOX6 in tumor cells, but only a few SOX6-positive cells were detected in nonneoplastic tissues from the cerebral cortex. These results indicate that the developmentally regulated transcription factor SOX6 may be a potential diagnostic marker for gliomas.
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PMID:Expression of a transcriptional factor, SOX6, in human gliomas. 1569 67

C/EBP beta (CCAAT/enhancer binding protein beta) is a transcriptional factor that belongs to the basic region-leucine zipper class DNA-binding proteins and plays a role in cell differentiation and inflammatory reactions. Although high tissue levels of inflammatory cytokines, such as interleukin (IL)-6, IL-8 and transforming growth factor-beta, have been observed in glioma patients, the mechanisms underlying this phenomenon remain to be elucidated. C/EBP beta induces a variety of cytokines and thus may play a role in the pathogenesis of glioma. In this study, we investigated the relationship between C/EBP beta expression, tumor histology, and prognosis in glioma. The expression of C/EBP beta mRNA was examined with quantitative real-time PCR and protein expression was examined with immunohistochemical techniques in 47 glioma tissue samples. Expression of C/EBP beta mRNA and protein was markedly increased in high grade glioma compared with low grade glioma. Patients whose expression of C/EBP beta mRNA and protein in tumor tissue was lower survived longer than those whose expressions were higher. In vitro, C/EBP beta siRNA inhibited glioma cell proliferation and invasion. Moreover, IL-8 production by glioma cells was inhibited by C/EBP beta siRNA transfection. These data suggest that increased expression of C/EBP beta may contribute to the promotion of tumor invasiveness and progression. The data imply that the comparison of C/EBP beta expression could be a prognostic marker for patients with glioma.
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PMID:Increased expression of CCAAT/enhancer binding protein beta correlates with prognosis in glioma patients. 1646 18

Malignant gliomas are characterized by active invasiveness, necrosis, and vascular proliferation. These pathological features have been speculated to be caused by tissue hypoxia. Hypoxia-inducible factor-1 (HIF-1), which is controlled by rapid stabilization of the HIF-1alpha subunit, is a pivotal transcriptional factor in the cellular response to hypoxia. Although many studies have described the relationship between tumor angiogenesis and hypoxic environment, the roles of HIF-1 in cell invasion have been barely elucidated in malignant gliomas. We investigated the role of HIF-1alpha in the motile and invasive activities of human glioma cells under hypoxia. Four malignant glioma cell lines, U87MG, U251MG, U373MG, and LN18, were cultured under 21 and 1% oxygen concentration. Expression of HIF-1alpha under hypoxia was observed to be much higher than that under normoxia in all cell lines. Introducing HIF-1alpha-targeted small interfering RNA (HIF-1alpha siRNA) into the glioma cell lines resulted in downregulation of HIF-1alpha expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with HIF-1alpha siRNA compared with those transfected with the control siRNA. Co-culture of glioma spheroids and rat brain slices showed that HIF-1alpha siRNA-transfected glioma cells failed to invade the surrounding normal brain tissue in an organotypic brain slice model. These effects of HIF-1alpha siRNA were more conspicuous under hypoxia than under normoxia. In addition, under hypoxic conditions, the level of matrix metalloproteinase (MMP)-2 mRNA was upregulated, and that of tissue inhibitor of metalloproteinase (TIMP)-2 was downregulated in all glioma cell lines. Treatment with HIF-1alpha siRNA resulted in downregulation of MMP-2 mRNA and upregulation of TIMP-2 mRNA. Furthermore, the enzyme activities of MMP-2 and MMP-9, both of which were activated by hypoxia, decreased with the introduction of HIF-1alpha siRNA. These findings suggest that overexpression of HIF-1alpha induced by hypoxic stress is an essential event in the activation of glioma cell motility through alteration of invasion-related molecules. Targeting the HIF-1alpha molecule may be a novel therapeutic strategy for malignant gliomas.
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PMID:Silencing hypoxia-inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas. 1733 17

TP53 is a key tumor suppressor gene that encodes a transcriptional factor involved in several cellular mechanisms, including growth arrest, DNA repair, and induction of apoptosis. In addition to TP53 gene mutations, a common polymorphism, Arg72Pro, has been involved in the carcinogenesis process. The Pro72 variant has been associated with a slower induction of apoptosis and may influence the risk of cancer development. The role of Arg72Pro polymorphism in glioma susceptibility is poorly characterized. With the objective of analyzing the role of the TP53 Arg72Pro polymorphism in glioma risk, overall survival, and patient therapy response in a Portuguese population, we conducted a retrospective case-control study, including 171 patients with gliomas and 526 cancer-free individuals. The Arg72Pro genotype was assessed by the polymerase chain reaction-restriction fragment length polymorphism technique. No statistically significant differences were observed in the genotypic and allelic frequencies between glioma and control groups, and no statistically significant differences were observed with stratification of gliomas into distinct histological subtypes: astrocytic (n = 115), glioblastoma (n = 75), and oligodendroglial (n = 54) tumors. No significant association was observed between TP53 Arg72Pro and patient overall survival, but Kaplan-Meier analysis of glioma patients harboring the Pro72 allele showed a significantly longer survival with adjuvant therapy. In this first assessment of the role of TP53 Arg72Pro polymorphism in a large series of Portuguese glioma tumors, no association was observed with glioma susceptibility or overall survival, except for patients submitted to adjuvant therapy.
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PMID:TP53 codon 72 polymorphism in susceptibility, overall survival, and adjuvant therapy response of gliomas. 1806 27


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