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 protein encoded by the proto-oncogene c-sis is over-amplified in human neuroglial tumors and has been hypothesized as playing an important role in tumorigenesis, but this hypothesis remains to be clarified. In order to address this issue, we examined the effect of 18-bp oligodeoxynucleotides complementary to the sense mRNA of c-sis upon glioma cell growth. First, we investigated the expression of c-sis protooncogenes within cultured human glioma cell lines and also fresh glioma specimens by using polymerase chain reaction. We could detect mRNA transcripts of c-sis in 3 out of 4 glioma cell lines (U138MG, U251MG and A172) and two in 5 glioblastoma multiforme specimens. The antisense oligonucleotides complementary to c-sis mRNA were efficiently incorporated into A172 in vitro and the kinetic study showed that maximum uptake occurred after 48 hours of incubation with antisense oligomers. Exposure of human glioma cell lines to antisense oligodeoxynucleotides targeted against first initiation codon inhibited cell proliferation in a time and dose dependent fashion. From the flow cytometric analysis using anti-c-sis sera, it was demonstrated that the antisense oligomers specifically block the de novo synthesis of intracellular c-sis protein by glioma cells dose-dependently. In contrast to this, the corresponding sense oligomers inhibited neither synthesis of c-sis protein nor glioma cell growth. Taken together, these results clearly support a role of c-sis protein in the proliferation process and show that inducible protein expression can be blocked by means of synthetic oligonucleotides complementary to a coding exon.
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PMID:[Inhibition of c-sis protein synthesis and cell growth with antisense oligonucleotides in human glioma cells]. 150 12

The AP1 transcriptional complex is a heterodimer composed of proteins encoded by the fos and jun proto-oncogene families. Changes in the concentration and composition of AP1 occur after cells are perturbed in a variety of different ways (Curran, in Reddy et al., eds. "The Oncogene Handbook," Amsterdam: Elsevier, pp 307-325, 1988; Sonnenberg et al., Neuron 3:359-365, 1989). Transient changes in AP1 content presumably result in altered expression of AP1-regulated target genes, that help to mediate the cell's long-term response to changes in its environment. One factor that may be important in determining which target genes are regulated by AP1 in a given context is the identity of the jun family member present in the complex (Chiu et al., Cell 59:979-986, 1989; Schutte et al., Cell 59:987-997, 1989). Fos induction has been demonstrated after binding of beta-adrenergic ligands to their cell surface receptors (Barka et al., Mol Cell Biol 6:2984-2989, 1986; Gubits et al., Mol Brain Res 6: 39-45, 1989; Arenander et al., J Neurosci Res 24: 107-114, 1989; Mocchetti et al., Proc Natl Acad Sci USA 86:3891-3895, 1989). However, the response of the jun gene family to this treatment has not been reported. We have therefore examined the effect of beta-adrenergic receptor activation on the expression of c-fos, c-jun, and junB mRNA levels in C6 glioma cells. Our results indicate that c-fos and junB mRNA levels are increased by 52- and 2.7-fold, respectively, after 45 min of isoproterenol (IPR) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic treatment of C6 glioma cells produces opposite changes in c-fos and c-jun mRNA levels. 168 82

Biopsy specimens of 19 human gliomas (10 glioblastomas, 2 anaplastic astrocytomas, 4 astrocytomas, one mixed glioma, one oligodendroglioma and one ependymoma) were examined for amplification of tumour-related genes located on chromosome 7: the proto-oncogene c-erb-B1 (encoding the epidermal growth factor receptor (EGFR], the proto-oncogene c-met, the platelet-derived growth factor A-chain gene, and the plasminogen activator inhibitor type-1 gene. Gene amplification was observed in 6 glioblastomas, and the EGFR gene was the only chromosome-7-gene examined that was amplified. The selective EGFR gene amplification in human glioblastomas suggests its potential role in the progression of some of these tumours.
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PMID:Amplification of the epidermal growth factor receptor gene in human gliomas. 177 45

Extracellular adenosine acts through specific cell surface receptors to modulate numerous physiological processes in both the CNS and peripheral tissues (e.g. neurotransmitter release and blood flow). Activation of A1 or A2 adenosine receptors leads to decreased or increased intracellular cAMP levels, respectively. Fos and Jun are nuclear proto-oncogene products, which, like cAMP, appear to act as intermediates in a number of signal transduction pathways. Since increases in both adenosine release and Fos and Jun expression occur in the brain following seizures, we wanted to determine whether Fos and Jun induction might occur as a result of adenosine receptor activation. 3T3 fibroblasts and NG108-15 neuroblastoma-glioma hybrid cells were chosen for study, since they were known to respond to adenosine agonists with changes in cAMP levels. The membranes of NG108-15 cells were shown to have A2-like binding activity in a competitive binding assay. Cultures of each cell line were treated with the adenosine agonists, CHA (A1-selective) and NECA (non-selective adenosine agonist). Both lines responded with a concentration-dependent transient increase in c-fos, but not c-jun, mRNA content after treatment with either agonist. The kinetics of the response were much more rapid for 3T3 cells (peak between 15 and 30 min) than for NG cells (peak between 60 and 90 min). The slower, more prolonged response in the NG108-15 cells is more similar to the time interval between adenosine release and the peak of c-fos mRNA induction in brains of animals following the administration of seizure-promoting drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of adenosine receptors induces c-fos, but not c-jun, expression in neuron-glia hybrids and fibroblasts. 217 6

Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.
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PMID:Cyclic AMP blocks expression of the c-sis gene in tumor cells. 254 92

Previously reported studies have suggested that variations in the pattern of proto-oncogene expression within a specific tumor type may denote an underlying difference in the biology and clinical behavior of those tumors. To more sensitively characterize malignant tumors of the central nervous system, we have used Northern blot hybridization analysis to determine the patterns of expression of seven proto-oncogenes in 20 cell lines established from biopsy specimens of patients with malignant glioma. The following proto-oncogenes are expressed at detectable levels in 30 micrograms of total RNA from most glioma cell lines examined: c-myc (20/20), c-mil/raf-1 (18/18), neu (19/20), c-erbB (19/20), and c-myb (17/20). In contrast, only half of the cell lines expressed detectable c-sis (10/20). In none of the cell lines tested was N-myc (0/20) mRNA detected. Morphologic analysis of these 20 cell lines revealed three different growth patterns: bipolar, epithelial, and pleomorphic-glial. Detectable levels of c-sis mRNA typically occurred with either an epithelial or pleomorphic-glial morphology. The pleomorphic-glial subgroup was also characterized by the expression of glial fibrillary acidic protein.
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PMID:Patterns of proto-oncogene expression in human glioma cell lines. 281 Mar 98

Stem cell factor (SCF), a hematopoietic growth factor, is the ligand of the tyrosine kinase receptor encoded by the c-kit proto-oncogene. Beside the important role of this receptor-ligand complex in hematopoiesis, gametogenesis and melanogenesis, SCF and its receptor have been shown to be expressed in the brain. We have studied the expression of SCF and c-kit in 20 human malignant glioma cell lines at the mRNA as well as at the protein level. In addition, recombinant human (rh) SCF was tested in [3H]thymidine uptake assays for a mitogenic effect on these cells. SCF and c-Kit proteins were detected in the cytoplasm of glioma cells by alkaline phosphatase-monoclonal anti-alkaline phosphatase immunostaining and Western blot analysis. However, neither SCF nor c-Kit were seen on the cell surface by flow cytometry. Furthermore, none of the proliferation assays showed a mitogenic effect for exogenously added rhSCF. Blocking studies using an anti-SCF antibody failed to demonstrate modulating effects on the growth of selected cell lines. These results suggest that SCF and c-Kit may mediate non-proliferative signals or may employ intracellular mechanisms for autocrine growth regulation of glioma cells.
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PMID:Coexpression of stem cell factor and its receptor c-Kit in human malignant glioma cell lines. 753 28

Colony stimulating factor 1 (CSF-1) is a functionally versatile, circulating homodimeric growth factor that stimulates the survival, proliferation, and differentiation of mononuclear phagocytic cells, the differentiation of osteoclast progenitor cells and that regulates cells of the female reproductive tract. CSF-1 is also expressed in the central nervous system where it may regulate the differentiation and activation of microglia. The diverse forms of CSF-1 are all encoded by a single gene. Alternative posttranscriptional splicing and posttranslational cleavage determines whether CSF-1 will be produced as a secreted proteoglycan, secreted glycoprotein, or as a cell-surface glycoprotein that may be involved in cell-cell interactions. CSF-1 is expressed in glioblastoma cell-lines, normal human astrocytes, and in operative specimens of human glioma. The CSF-1 receptor, encoded by the c-fms proto-oncogene, is also expressed in human gliomas. We conclude that coexpression of CSF-1 and its receptor in some human gliomas hints at a possible autocrine or paracrine growth stimulatory role for CSF-1; however, its function in the mammalian CNS remains to be elucidated.
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PMID:Colony stimulating factor-1 expression in human glioma. 808 34

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


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