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)

The expression of the gene encoding the rat beta 1-adrenergic receptor is suppressed by glucocorticoids (Kiely et al., 1994). Within the 3.2-kb 5'-flanking region of the promoter, two potential glucocorticoid response elements (GREs) at -950 and -2791 relative to the translational ATG were identified. Characterization of the glucocorticoid-responsive sequences in the 5'-flanking region of the beta 1-adrenergic receptor gene was explored in rat C6 glioma cells and human HepG2 hepatoma cells using transient expression of beta 1-adrenergic receptor-luciferase fusion genes. The ability of glucocorticoids to suppress luciferase expression was not altered when the most 5'-localized GRE was deleted. Deleting the potential GRE at -950, in contrast, abolished glucocorticoid-induced suppression of the beta 1-adrenergic receptor-luciferase gene transcription. A 25-bp element containing the GRE sequence between nucleotides -950 and -926 confers glucocorticoid-dependent inhibition of transcription to a neutral promoter. Gel mobility shift assays with the alpha-subunit of the human glucocorticoid receptor (hGR alpha) expressed in reticulocyte lysates demonstrated specific binding to the 25-bp sequence harboring the putative GRE. We report an inhibitory GRE in the promoter of the rat beta 1-adrenergic receptor gene that is conserved among the rat, human, and mouse genes.
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PMID:Identification of a glucocorticoid repressor domain in the rat beta 1-adrenergic receptor gene. 925 49

The interaction of urokinase-type plasminogen activator (uPA) with its cell-surface receptor (uPAR) is implicated in diverse biological processes such as cell migration, tissue remodeling, and tumor cell invasion. Recent studies indicated that uPAR can act as an extracellular matrix receptor during cell adhesion. Recently, we showed that transfection of the human glioma cell line SNB19 with antisense uPAR resulted in downregulation of uPAR at both the mRNA and protein levels. In this study, we used SNB19 to determine how the presence or absence of uPAR promotes cell spreading and associated changes in cell morphology. Microscopic analysis of cell spreading revealed that antisense uPAR-transfected cells were larger, remained round, and did not spread efficiently over extracellular matrix substrate type IV collagen and fibronectin, unlike parental SNB19 cells, which were smaller and spindle shaped. Biochemical studies showed that antisense uPAR-transfected cells, in addition to not spreading, exhibited increased expression of alpha 3 beta 1 integrin but not alpha 5 beta 1 integrin. However, we could not find a change in the expression of extracellular matrix components or altered growth rate in these cells. Furthermore, despite the increased alpha 3 beta 1 integrin expression, antisense uPAR-transfected cells failed to form an organized actin cytoskeleton when plated on type IV collagen or fibronectin, unlike parental SNB19 cells, which displayed an organized cytoskeleton. These findings show that the absence of uPAR in human glioma cells leads to morphological changes associated with decreased spreading and a disorganized cytoskeleton resulting in altered cell morphology, suggesting that coordinated expression of uPAR and integrin may be involved in spreading of antisense uPAR-transfected glioma cells.
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PMID:Altered in vitro spreading and cytoskeletal organization in human glioma cells by downregulation of urokinase receptor. 943 80

Numerous in vivo methodologies have documented the invasive behavior of glioma cells through normal brain parenchyma. Glioma cell locomotion has also been assessed with a number of in vitro assays including the Boyden chamber and other chemotaxis assays, colloidal gold cell tracking, analysis of migration of cells tumor cells from spheroids, confrontation cultures of glioma cells with aggregates of non-neoplastic tissue, time-lapse video microscopy, electron microscopic examination of the cytomorphologic correlates of cell motility, the radial dish assay, and quantitative enzyme immunoassay of proteins associated with invasion (e.g. laminin). Several of these techniques have been specifically modified to assess the effects of cytokines on glioma cell motility in vitro. Cytokines studied utilizing these methods include: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), the bb dimer of platelet-derived growth factor (PDGFbb), nerve growth factor (NGF), interleukin 2 (IL-2), transforming growth factors alpha and beta 1 (TGF alpha and TGFstraat1), and tumor necrosis factor alpha (TNF alpha). This review summarizes the investigational methods used to evaluate random and directional glioma cell motility and invasion in vivo and in vitro. The roles of specific mitogens as motogens, as evaluated with these methods are then presented.
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PMID:Mitogens as motogens. 944 23

Within the brain, dissemination of glioma cells follows myelinated fiber tracts and extracellular matrix containing structures such as the basement membranes of blood vessels. These patterns represent the two major routes of invasion frequently observed in clinical disease. Previously, we have characterized the substrates for preferential glioma adhesion and migration on purified ECM protein. In this study sections of human brain from different anatomical regions were used as adhesive substrates and also characterized for the presence and distribution of matrix proteins. Adhesion of marker gene transfected glioma cell suspensions to different regions and anatomical structures of human brain was quantified using a computer assisted image analysis system. Monoclonal antibodies against different adhesion molecules were used to inhibit glioma cell attachment ot specific anatomical structures. In addition, glioma cell aggregates were allowed to adhere to brain sections and single cells were observed to migrate out of these aggregates. Scanning electron microscopy was used to morphologically study the preferred routes of glioma dissemination on brain sections. In brain sections different kinetics of cell adhesion to distinct structures were observed. Within 15 minutes cells adhered and spread on blood vessels and arachnoid tissue containing sections. Choroid plexus and the ventricular wall were also adhesive structures. Adhesion to cortex required 1 hour, while adhesion and spreading on myelinated fiber tracts was retarded and required several hours of incubation. The predominant matrix proteins in small vessels were found to be laminin, collagen type IV, and fibronectin. Choroid plexus and the ependyma showed a similar composition of matrix proteins. Arachnoid fibers contained different types of collagens, predominately type I and III, whereas the only matrix protein identified in the subependyma was fibronectin. Antibodies to the alpha 2, alpha 3, and beta 1 integrin subunits completely blocked adhesion to arachnoid tissue, anti-NCAM inhibited attachment to cortex. Adhesion to blood vessels in brain sections could only be inhibited to 50% by anti-integrin beta 1. Antibodies to the av containing integrin av beta 3 also blocked 50% of adhesion to vessels. Our findings indicate that adhesion of glioma cells to brain sections most rapidly takes place on ECM protein containing regions, especially blood vessels which may serve as guiding structures for glioma dissemination.
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PMID:Glioma cell adhesion and migration on human brain sections. 970 90

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.
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PMID:Chemical, metabolic and immunological characterization of gangliosides of human glioma cells. 992 80

Hydrogen peroxide has been suggested to play an important role in the pathogenesis of Alzheimer's disease. In the present study, the effects of hydrogen peroxide upon the functional integrity of beta-adrenoceptors have been investigated in C6 glioma cells. Treatment of cells for 24 h with hydrogen peroxide in serum-free medium produced a concentration-dependent cell toxicity, seen both using cell counting and LDH release into medium as end point. There were no large nor consistent changes in either the density of cell surface beta 1, or beta 2-adrenoceptors, measured using the hydrophilic ligand [3H](-)-CGP 12177, nor in either basal, forskolin and isoprenaline-stimulated cAMP responses, following hydrogen peroxide treatment. It is concluded that the decreased adenylyl cyclase activity and responsiveness to Gs stimulation found in post-mortem brain samples from Alzheimer's disease autopsy cases is unlikely to be mediated by hydrogen peroxide.
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PMID:The effect of hydrogen peroxide upon beta-adrenoceptor density and function in C6 rat glioma cells. 1010 Jan 97

Laminin-10/11, the laminin isoforms containing the alpha 5 chain, are major components of basement membranes of many fetal and adult tissues. Laminin-10/11 purified from the conditioned medium of human lung carcinoma cells were potent in mediating adhesion of the carcinoma cells in an integrin alpha 3 beta 1-dependent manner. To further define the type(s) of integrins involved in cell adhesion to laminin-10/11, we examined the effects of a panel of function-blocking anti-integrin antibodies on the adhesion of different cell types to laminin-10/11. Although anti-integrin beta 1 antibody inhibited the adhesion of all cell types tested, anti-alpha 3 antibody inhibited the adhesion of carcinoma and glioma cells but not fibroblastic cells. Adhesion of fibroblastic cells was inhibited, however, by a combination of anti-alpha 3 and anti-alpha 6 antibodies, suggesting that both alpha 3 beta 1 and alpha 6 beta 1 integrins function as laminin-10/11 receptors in these cells. To explore this possibility, we examined the adhesion of K562 leukemic cells transfected with integrin alpha 3 or alpha 6 subunit to laminin-10/11 or other laminin isoforms. Laminin-10/11 were potent adhesive ligands for both the alpha 3 beta 11 and alpha 6 beta 1 transfectants, whereas laminin-5 was the preferred ligand for the alpha 3 beta 1 transfectants. Upon stimulation with the activating anti-integrin beta 1 antibody, both transfectants became more adherent to the substratum regardless of the type of laminins coated, although their preference for laminin isoforms remained unaltered. K562 cells transfected with alpha 6 and beta 4 subunits were also capable of adhering to laminin-10/11, indicating that integrin alpha 6 beta 4 is another receptor for laminin-10/11. Even with lung carcinoma cells, the alpha 6-containing integrins partly contributed to adhesion to laminin-10/11 at higher coating concentrations, although non-integrin receptor(s) might also be involved under such conditions. These results indicated that laminin-10/11 are potent and versatile adhesive ligands in basement membranes capable of binding to both alpha 3 beta 1 and alpha 6 beta 1 integrins with high avidity and also to alpha 6 beta 4 integrin.
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PMID:Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins. 1067 76

beta 1-Adrenergic receptors (beta1-ARs) serve as important regulators of central nervous system (CNS)-mediated behavior and several neural functions, including mood, memory, neuroendocrine control, and stimulation of autonomic function. Using beta 1-AR-luciferase reporter recombinants, we have previously determined that important beta 1-AR genetic elements controlling expression within the C6 glioma cell line are contained within the region -396 to -299, relative to the translational start site. By conducting progressive internal deletions of the rat beta 1-AR 5' flanking region and with the use of beta 1-AR-luciferase recombinants, we have verified that this region contains the primary beta 1-AR promoter and/or major regulatory elements. To begin the identification of protein factors involved in beta 1-AR transcriptional activity conferred by this beta 1-AR region and flanking sequences, we conducted electrophoretic mobility shift assays using defined beta 1-AR DNA subregion probes. One probe (GS-1), encompassing the region -396 to -367, was found to produce two major and two minor mobility shift complexes when bound to nuclear extracts from the beta 1-AR expresser C6 cell line. UV-crosslinking of DNA-protein complexes, coupled with DNase I digestion, indicated that this beta 1-AR region interacts with one major protein of approximately 117 kDa molecular weight and additional minor proteins. GS-1 DNA-protein complexes were observed using beta 1-AR expresser tissues in the CNS, including cortex, hippocampus, and olfactory bulb. No DNA-protein complexes were observed when using nuclear extracts from beta 1-AR nonexpresser tissues; in some cases, using L6 cells, previously characterized to express little or no beta1-ARs, a reduction in intensities of the DNA-protein complexes was observed. Competition experiments indicate that nuclear protein binds to one of two subregions within the GS-1 sequence that contain AP-2-like consensus elements. Recombinant AP-2 protein will bind to both the beta 1-AR GS-1 promoter fragment and commercially available AP-2 consensus element control probes. Interestingly, using antibody supershift and immunoblotting experiments, no supershifts were observed and the major 117-kDa protein was not immunoreactive to antibodies recognizing either AP-2 alpha or AP-2 beta. These results support our contention that this beta 1-AR regulatory region contains AP-2 consensus elements that recognize novel transactivator proteins.
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PMID:Rat beta 1-adrenergic receptor regulatory region containing consensus AP-2 elements recognizes novel transactivator proteins. 1086 Aug 67

Effects of ionising radiation on extracellular matrix (ECM)-modulated cell survival and on adhesion and invasion are not well understood. In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue. To examine these effects in more depth, four human glioblastoma cell lines (A-172, U-138, LN-229 and LN-18) were irradiated on fibronectin (FN), Matrigel, BSA or polystyrene. Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA. Irradiation induced a dose-dependent increase in functional beta 1- and beta 3-integrins in all four glioma cell lines. This integrin induction caused improved cell adhesion to FN or Matrigel. In contrast to U-138, LN-229 and LN-18 cells, irradiation strongly impaired A-172 cell invasion. Invasion of all cell lines was inhibited by anti-integrin antibodies, the disintegrin echistatin and the MMP-2/-9 inhibitor III. Additionally, beta 1- and beta 3-integrins modulated basal and radiation-altered gelatinolytic activity of MMP-2. Tested glioblastoma cell lines showed a differential cellular susceptibility to FN or Matrigel which affected the cellular radiosensitivity. Three out of four glioma cell lines demonstrated a combination of a substratum-independent survival after irradiation and an invasive potential which was not affected by irradiation. beta 1- and beta 3-integrins were identified to play a substantial, regulatory role in survival, adhesion, invasion and MMP-2 activity. Detailed insights into radioresistance and invasion processes might offer new therapeutic strategies to enhance cell killing of lethal high-grade astrocytoma.
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PMID:Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines. 1464 48

Radiotherapy is an important treatment for patients suffering from high-grade malignant gliomas. Non-targeted (bystander) effects may influence these cells' response to radiation and the investigation of these effects may therefore provide new insights into mechanisms of radiosensitivity and responses to radiotherapy as well as define new targets for therapeutic approaches. Normal primary human astrocytes (NHA) and T98G glioma cells were irradiated with helium ions using the Gray Cancer Institute microbeam facility targeting individual cells. Irradiated NHA and T98G glioma cells generated signals that induced gammaH2AX foci in neighbouring non-targeted bystander cells up to 48 h after irradiation. gammaH2AX bystander foci were also observed in co-cultures targeting either NHA or T98G cells and in medium transfer experiments. Dimethyl sulphoxide, Filipin and anti-transforming growth factor (TGF)-beta 1 could suppress gammaH2AX foci in bystander cells, confirming that reactive oxygen species (ROS) and membrane-mediated signals are involved in the bystander signalling pathways. Also, TGF-beta 1 induced gammaH2AX in an ROS-dependent manner similar to bystander foci. ROS and membrane signalling-dependent differences in bystander foci induction between T98G glioma cells and normal human astrocytes have been observed. Inhibition of ataxia telangiectasia mutated (ATM) protein and DNA-PK could not suppress the induction of bystander gammaH2AX foci whereas the mutation of ATM- and rad3-related (ATR) abrogated bystander foci induction. Furthermore, ATR-dependent bystander foci induction was restricted to S-phase cells. These observations may provide additional therapeutic targets for the exploitation of the bystander effect.
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PMID:ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. 1690 3


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