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)

Northern blot and ribonuclease protection assay were used to identify alpha 2-adrenoceptor subtypes in human colonic adenocarcinoma (HT29), neuroblastoma x glioma rat-mouse hybrid NG108-15 (NG108) and opossum kidney (OK) cell lines. Radioligand binding studies showed that the alpha 2-adrenoceptor expressed in HT29, NG108 and OK cells represent the pharmacological alpha 2A, alpha 2B and alpha 2C subtypes respectively. In our Northern blot analysis, hybridization of poly(A)+ RNA from HT29, NG108 and OK cells with human kidney alpha 2-adrenoceptor cDNA probe (alpha 2-C4) identified a single band of 4.4, 4.2 and 4.4 kb respectively in each cell line. Hybridization with a human platelet alpha 2-adrenoceptor genomic probe (alpha 2-C10) resulted in two bands for HT29 cells with the size of 4.4 kb and 3.9 kb. No bands were seen for HT29, NG108 and OK cells when hybridized with a third alpha 2-adrenoceptor human genomic DNA probe which is localized in chromosome 2 (alpha 2-C2). For the HT29 cells, the 3.9 kb band was seen only when using the alpha 2-C10 probe. Thus, this band probably represents alpha 2-C10 mRNA. To further characterize the alpha 2-adrenoceptor mRNA expressed in HT29, NG108 and OK cells, the sensitive ribonuclease protection assay was performed. A single band about 900 bp was protected when the poly(A)+ RNA from NG108 and OK cells was hybridized with an alpha 2-C4 RNA probe and digested with RNAases. Hybridization of mRNA from HT29 cells with alpha 2-C10 RNA probe and digestion with RNAases protected a 500 bp fragment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Northern blot and ribonuclease protection study of alpha 2-adrenoceptor subtypes in cultured cell lines. 132 48

The growth of rat glioma C6 cells, which provide an in vitro model of glial cells, is inhibited by retinoic acid and glucocorticoids, two agents which are important in brain differentiation and growth. To determine whether the growth-inhibitory effects of these agents are mediated by alterations in insulin-like growth factor I (IGF-I) production, the effects of retinoic acid and dexamethasone on IGF-I production and messenger RNA levels in C6 cells were investigated. IGF-I mRNA levels were determined using a solution hybridization/RNase protection assay. Treatment of C6 cells with dexamethasone or retinoic acid decreased IGF-I mRNA levels in a time-dependent fashion. The time course of the effect of the two agents differed, with the peak effect of dexamethasone between 6 and 12 h and the peak effect of retinoic acid at 27 h. In dose-response studies, IGF-I mRNA levels decreased to 27% of control levels (cells maintained in serum-free media) after treatment with 5 ng/ml dexamethasone, while half-maximal inhibition was achieved with approximately 0.5 ng/ml (1.4 nM) dexamethasone. Treatment with 10 microM retinoic acid decreased IGF-I mRNA levels to 24% of control levels with half-maximal inhibition occurring with approximately 0.5 microM retinoic acid. Cycloheximide prevented the inhibitory effect of these agents on IGF-I mRNA levels, suggesting that their effect is at least partly dependent upon protein synthesis. Immunoreactive IGF-I levels in media conditioned for 48 h by cells treated with dexamethasone or retinoic acid decreased to 32% and 42% of control levels, respectively. Treatment of C6 cells with retinoic acid or dexamethasone decreased thymidine incorporation into DNA. Treatment of cells with IGF-I alone had no effect on thymidine incorporation into DNA, but addition of 10 or 50 ng/ml IGF-I to dexamethasone-treated cells stimulated a small, but significant (P less than 0.01), increase in thymidine incorporation into DNA. IGF-I was not, however, able to reverse the inhibitory effect of retinoic acid. Finally, treatment of cells with 150 ng/ml of IGF binding protein 1 significantly decreased (P less than 0.01) thymidine incorporation into DNA by 17% as compared to incorporation into control cells maintained in serum-free media.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of insulin-like growth factor I production in rat C6 glioma cells: possible role as an autocrine/paracrine growth factor. 157 88

In a group of four human tumor cell lines comprising one melanoma, one glioma, one teratocarcinoma and one neuroblastoma, the expression of the intercellular adhesion molecule-1 (ICAM-1) was found to be significantly increased following treatment with 10 microM of all-trans retinoic acid. In the melanoma and glioma cell lines HS 294T and HS 683, greater than 90% of the cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) CL203.4 in the absence of treatment. Retinoic acid increased the cell surface expression of the molecule by 2-fold. In the teratocarcinoma and neuroblastoma cell lines, TERA-2 and SK-N-SH, the constitutive expression of ICAM-1 was weak, the percentage of cells stained above the background being less than 25%. Retinoic acid induced ICAM-1 expression in greater than 80% of the cells and increased the levels of expression by 2.5 to 3-fold. Immunoprecipitation studies in biosynthetically labeled cells as well as RNase protection analysis confirmed that retinoic acid treatment increased the amount of ICAM-1 at both the protein and mRNA level. The induction or stimulation occurred within 24 h, was maximal after 4 days and reversible.
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PMID:Regulation by retinoic acid of ICAM-1 expression on human tumor cell lines. 168 Mar 99

Two major classes of mRNAs for the alpha-crystallin B chain (or alpha(B)crystallin), about 0.9 and 1.2 kilobases in length, are expressed in rat brain. To examine the structures of these mRNAs, we isolated cDNA clones from rat brain and genomic DNA from rat liver. Characterization of these clones as well as Northern blot analysis indicated that the various mRNAs differed in the lengths of their 5' leader sequences. RNase protection assays revealed that the gene for alpha-crystallin B chain contains multiple start sites. The transcriptional start sites of the longer mRNAs are preceded by a putative CAAT box and that of the shorter mRNA by a putative TATA box. The shorter mRNA encodes the alpha-crystallin B chain protein, whereas the longer mRNA contained three extra small open reading frames upstream of the AUG start codon for the protein. The shorter mRNA is abundant in lens, heart, muscle, and kidney, while the longer mRNAs are constitutively expressed at low levels in a wide variety of tissues. The shorter mRNA was increased by treatment with phorbol 12-myristate 13-acetate in rat C6 glioma cells. Since there is only a single copy of the alpha-crystallin B chain gene, our results indicate that the two classes of mRNAs are generated by alternative transcriptional initiation from different promoters and their expressions are regulated differentially.
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PMID:Multiple mRNAs of rat brain alpha-crystallin B chain result from alternative transcriptional initiation. 217 7

Evidence is presented that isoproterenol treatment of rat C6 glioma cells, under conditions that increase glioma cell cAMP levels, causes the phosphorylative modification of several RNA polymerase II subunits. RNA polymerase II in control and isoproterenol-stimulated 32Pi-labeled confluent glioma cells was immunoprecipitated from ribonuclease-treated nuclear extracts with hen anti-calf RNA polymerase II antiserum conjugated to Sepharose. The immunoprecipitated RNA polymerase II was analyzed for 32P-labeled subunits by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. Using this technique, we have shown that isoproterenol causes a time-dependent increase of phosphate incorporation into RNA polymerase II subunits of 214,000, 180,000, 140,000, 35,000, 28,000, and 16,500 daltons. Phosphate incorporation occurred exclusively on serine in all of the six subunits. About 0.5-2 mol of phosphate/mol of RNA polymerase II subunit were incorporated. Dibutyryl cAMP (10(-3)M) mimics the stimulatory action of isoproterenol and mediates increased phosphate incorporation into the six subunits. (RS)-propranolol (10(-4)M) prevents the isoproterenol-mediated phosphorylative changes. These data indicate that isoproterenol, via cAMP, mediates a transient structural modification of RNA polymerase II subunits in rat C6 glioma cells which may possibly lead to a modulation of RNA polymerase II function(s).
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PMID:Phosphorylation of rat C6 glioma cell DNA-dependent RNA polymerase II in vivo. Identification of phosphorylated subunits and modulation of phosphorylation by isoproterenol and N6,O2'-dibutyryl cyclic AMP. 609 70

Molecular processes resulting in the malignant transformation from low- to high-grade astrocytoma remain poorly understood. Using reverse transcriptase PCR, we identified a gene that is differentially expressed in normal brain and low-grade astrocytoma compared to glioblastoma tissues. This gene is identical to human beta 2-chimaerin, which encodes a 468-amino acid GTPase-activating protein for p21rac. The gene was localized to human chromosome 7p15.3 by fluorescence in situ hybridization mapping. Human beta 2-chimaerin is expressed in a variety of human tissues, with the highest expression level detected in human brain and pancreas. RNase protection assays indicated that the expression level of this gene is high in all the normal brain and low-grade astrocytoma samples tested compared to malignant gliomas. The down-regulation of beta 2-chimaerin expression in the high-grade gliomas suggests that decreased expression of this gene may be a feature of progression in the development of malignant glioma.
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PMID:Identification and characterization of human beta 2-chimaerin: association with malignant transformation in astrocytoma. 761 86

We have characterized the 5' and 3' ends of the rat beta 1-adrenergic receptor transcript using RNase protection assays and have used transient transfection analysis to identify regions of the beta 1-adrenergic gene 5'-flanking sequences which are important for expression. The transcript has multiple start sites, occurring primarily in two clusters at bases -250 and -280, relative to the first base of the initiation codon. Two potential polyadenylation signals at +2450 and +2732 are both functional, although the site at +2732 is preferred both in C6 glioma cells and in heart tissue. Characterization of the gene by transient transfection analysis has identified a region between bases -389 and -325 which is necessary for expression. The specific deletion of a potentially functional inverted CCAAT sequence within this region does not significantly alter activity. In addition to the region from -389 and -325, deletion of the bases between -1 and -159 and between -186 and -211 significantly alters expression. Both of these regions are down-stream from the beta 1-adrenergic receptor gene start sites and may function either through regulation of transcription or through alteration of the transcript structure.
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PMID:Transcription of the rat beta 1-adrenergic receptor gene. Characterization of the transcript and identification of important sequences. 781 67

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

The first three exons and the promoter of rat glia-derived nexin, also called protease nexin-1 (GDN/PN-1), have been identified through analysis of rat genomic clones. A 1.6 kilobase (kb) fragment containing 105 base pairs of the first exon and 5'-flanking sequences was sequenced. The 5'-flanking sequence and the first exon were found to be GC-rich, indicating that the 5' region of the rat GDN/PN-1 gene resides within a CpG island. A TATA box-like sequence, but no CAAT box, was found. The rat GDN/PN-1 promoter contains five SP1 consensus sites, four consensus sites for the MyoD1 transcription factor, and one binding site for the transcription factors NGFI-A, NGFI-C, Krox-20, and Wilms tumor factor. The presence of these consensus sequences is consistent with the known expression pattern of GDN/PN-1. Primer extension and RNase protection assays identified one transcriptional start site. The 1.6 kb promoter fragment cloned in a reporter plasmid was found to induce firefly luciferase expression in a cell-specific manner. A positive regulatory element is localized in the region -1545 to -389. In vitro CpG methylation blocked transcription from the GDN/PN-1 promoter in rat hepatoma cells but not in C6 rat glioma cells.
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PMID:Molecular organization of the rat glia-derived nexin/protease nexin-1 promoter. 826 20

Onconase, or P-30, is a protein initially purified from extracts of Rana pipiens oocytes and early embryos based upon its anticancer activity both in vitro and in vivo. It is a basic single-chain protein with an apparent molecular mass of 12,000 daltons and is homologous to RNase A. In cultured 9L glioma cells, onconase inhibits protein synthesis with an IC50 of about 10(-7) M. The inhibition of protein synthesis correlates with cell death determined by clonogenic assays. 125I-Labeled onconase binds to specific sites on cultured 9L glioma cells. Scatchard analysis of the binding data shows that onconase appears to bind to cells with two different affinities, one with a Kd of 6.2 x 10(-8) and another of 2.5 x 10(-7) M. Each cell could bind about 3 x 10(5) molecules of onconase at each of the two affinity sites. The low affinity Kd is similar to the IC50 for onconase toxicity. Onconase also demonstrates a saturability of cytotoxicity at a concentration that would saturate the low affinity binding site. Incubation at 4 degrees C increased the binding of onconase to cells relative to 37 degrees C binding and also increased the sensitivity of cells to onconase toxicity, indicating that receptor binding may be an initial step in cell toxicity. Onconase cytotoxicity can be blocked by metabolic inhibitors, NaN3 and 2-deoxyglucose, and cytotoxicity is potentiated 10-fold by monensin. Ribonuclease activity appears necessary for onconase toxicity because alkylated onconase, which only retains 2% of the ribonuclease activity, was at least 100-fold less potent in inhibiting protein synthesis in cells. Onconase inhibition of protein synthesis in 9L cells coincides with the degradation of cellular 28 S and 18 S rRNA. In contrast to RNase A, onconase is resistant to two RNase inhibitors, placental ribonuclease inhibitor and Inhibit-Ace. Northern hybridization with placental ribonuclease inhibitor cDNA probe indicates that 9L glioma cells contain endogenous placental ribonuclease inhibitor mRNA. Based on these results, we propose that onconase toxicity results from onconase binding to cell surface receptors, internalization to the cell cytosol where it degrades ribosomal RNA, inhibiting protein synthesis and causing cell death.
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PMID:A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. 848 18


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