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)

ST1, a hydrocortisone-hypersensitive variant of the C6 rat glioma cell line, produced viral particles upon treatment with this glucocorticoid hormone. The virus was identified as type C RNA tumor virus by: a) morphology; b) 3H-uridine labelling; c) banding in sucrose density gradient; d) reverse transcriptase activity. Hydrocortisone uniquely shut off ST1 cells' transformed phenotype and turned on viral particles production.
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PMID:RNA tumor virus production accompanies the transformed phenotype change induced by hydrocortisone hormone in rat glioma cells. 662 5

1. Hydrocortisone, a glucocorticoid hormone, renders C6 rat glioma cells (clone ST1) sensitive to a block by colchicine or nocodazole (microtubule disrupters) at the G1 phase of the cell cycle. Restimulation of DNA synthesis in hydrocortisone-treated glioma cells arrested at G0/G1 phase by serum step-down is inhibited (85%) by colchicine (0.4 microgram/ml) added during the first 6 h of restimulation by serum step-up. 2. Exponentially growing, hydrocortisone-treated glioma cell cultures when subjected to colchicine treatment accumulated mitoses for 16.5 h, resulting in two types of cell cycle blocked cells: mitotic (round, detached or poorly attached) and G1 phase cells (flat and well attached to the solid substrate). The latter reinitiated DNA synthesis 15 h after colchicine withdrawal. Plating efficiency assays showed that while the colchicine block was highly toxic for mitotic cells, the survival of G1 phase arrested cells was not affected. In conclusion, in these rat glioma cells, hydrocortisone reversibly makes G1 phase progress dependent on microtubule integrity. 3. Restimulation of DNA synthesis in "normal" 3T3 fibroblasts arrested at the G0/G1 phase by serum deprivation was not inhibited by colchicine when the drug was added at the time of serum step-up. However, 70% inhibition occurred when colchicine was added at 10 h of serum stimulation.
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PMID:Glucocorticoid hormone renders a rat glioma cell line sensitive to a G1 phase block by microtubule disrupting agents. 718 25

Glucocorticoid hormones modulate the actions of peptide growth factors and constitute important therapeutic tools as anti-inflammatory and anti-tumor agents. The C6 rat glioma cell line responds to glucocorticoids with changes in morphology and growth block. The hyper-responsive ST1 cell variant displays a dramatic phenotypic reversion under the influence of these hormones. Thus, the transformed and tumorigenic cells reversibly change to a normal and non-tumorigenic phenotype. In addition, the cells also produce a C-type retrovirus. We used poly A+ mRNA from ST1 cells that had been treated with hydrocortisone to generate a cDNA library that was then screened, by differential hybridization, for glucocorticoid-responsive cellular sequences. The retroviral genomic RNA was used to generate a viral-specific probe. Cross hybridization led to the isolation of at least 4 cDNA clones of which 3 are cellular sequences and one corresponds to a retroviral gene. These clones were characterized by DNA sequencing and Northern blot hybridization analysis.
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PMID:Glucocorticoid-regulated gene in transformed to normal phenotypic reversion. 808 Dec 79

The C6 rat glioma cell line is response to glucocorticoid hormones. C6 variants that are hyper-responsive (ST1) and resistant (P7) to hormone treatment have been derived previously. Glucocorticoid treatment of ST1 cells leads to complete reversion of the transformed phenotype and loss of tumorigenic potential. Production of C type retrovirus particles is also induced by glucocorticoids in ST1 cells. Cloning of the genes regulated by glucocorticoids in this cell system was used here as a strategy to uncover the gene products involved in the transformed-to-normal phenotypic change. Construction of a cDNA library from glucocorticoid-treated ST1 cells and screening by differential hybridization resulted in the isolation of three cellular sequences that code for rat metallothioneins (C27 and C41) and alpha 1-acid glycoprotein (C36). Northern blot analysis revealed that expression of these genes was dramatically induced by hydrocortisone in ST1 but not in P7 cells. Viral genomic RNA was used to isolate and characterize retrovirus-related sequences that could also be responsible for the phenotypic reversion phenomenon.
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PMID:Cloning of glucocorticoid-regulated genes in C6/ST1 rat glioma phenotypic reversion. 856 57

A number of gene products involved in the control of cell proliferation fall into one of two classes: oncogenes and tumor suppressor genes. The same gene products have also been associated with malignant growth (tumors) caused by radiation, chemicals and tumor viruses. Here we describe our attempts to elucidate the molecular mechanisms underlying polyomavirus-induced cell transformation and the anti-tumor activity of glucocorticoid hormones. Wild type and mutant polyomavirus middle T (MT) overexpressing cell lines, generated with retroviral vector constructs, were used to investigate the role played by peptide growth factor primary response genes (fos, jun, myc, JE, KC) in viral transformation and to map the transduction pathway of the mitogenic signal of MT. Overexpression of MT leads to increased AP-1 (Fos/Jun) transcriptional complex activity. Transformation defective mutant analysis allowed the identification of sites in the MT molecule that are crucial for this activity. Two different approaches were used to investigate the molecular basis for glucocorticoids anti-tumor activity, namely: blind cloning of cDNAs and analysis of growth control genes in C6 glioma cell variants that are either hypersensitive (C6/ST1) or unresponsive to glucocorticoids (C6/P7). Four different glucocorticoid-regulated cDNA sequences were isolated using differential hybridization. A number of differentially expressed sequences were isolated from glucocorticoid-treated C6/ST1 cells by differential display (DDRT-PCR) and are currently being characterized. Expression of known growth control genes in C6/ST1 cells allowed the identification of important candidates for glucocorticoid hormone targets.
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PMID:Molecular genetic approach to cell proliferation control and neoplasia. 907 Mar 80

We have previously described a dramatic phenomenon of phenotypic reversion (tumor to normal) caused by glucocorticoid hormones in C6/ST1 rat glioma cells, but not in their hormone-resistant C6/P7 counterpart. Blind cDNA cloning was adopted to search for glucocorticoid-regulated gene sequences responsible for this phenotype reversion. Differential hybridization and differential display of RNA were used in parallel to isolate a number of cDNA clones that were characterized by DNA sequencing and Northern blot analysis. This approach was coupled to the analysis of known growth control genes (oncogenes, tumor suppressor genes, cyclins, cyclin-dependent kinases, other kinases). Glucocorticoid target genes isolated from this cell system are likely to be good anti-tumor candidate molecules which can be used in tumor therapy and anti-tumor drug design.
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PMID:Use of cDNA cloning to study the mechanism of action of glucocorticoid hormones at the molecular level. 922 40

Treatment of ST1 rat glioma cells with glucocorticoid hormones leads to complete reversion of their transformed phenotype and loss of their tumorigenic potential. In order to study the molecular basis of the anti-tumor activity of these hormones, we isolated glucocorticoid-regulated cDNA sequences associated with ST1 cells' phenotypic reversion, using suppression subtractive hybridization (SSH). DNA sequencing of the subtracted cDNA pool, cloned into the pBluescript vector, revealed three widely expressed, well known negative growth regulators, namely, thrombospondin 1, cyclin G and tyrosine phosphatase CL100, as primary targets of glucocorticoid hormones. Additionally, a gene recently described in human brain, NRP/B (nuclear restricted protein in brain) that associates with p110Rb in induction of neuronal differentiation and a new truncated transcript of the tenascin-X gene family, are also shown to be up-regulated by glucocorticoids. The products of these genes are strong candidates to be important players in glucocorticoids anti-tumor activity.
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PMID:Isolation and characterization of genes associated with the anti-tumor activity of glucocorticoids. 1239 65

Glucocorticoid hormones (GCs) exert a potent anti-proliferative activity on several cell types. The classic molecular mechanism of GCs involves modulation of the activity of the glucocorticoids receptor, a transcriptional regulator. However, the anti-proliferative effect of GCs may also involve modulation of processes such as translation, subcellular localization and post-translational modifications, which are not reflected at the mRNA level. To investigate these potential effects of GCs, we employed the proteomic approach (two-dimensional electrophoresis and mass spectrometry) and the ST1 cells, obtained from the C6 rat glioma cell line, as a model. GC treatment leads ST1 cells to a complete transformed-to-normal phenotypic reversion and loss of their tumorigenic potential. By comparing sets of 2D nuclear protein profiles of ST1 cells treated (or not) with hydrocortisone (Hy), 13 polypeptides displaying >or=two-fold difference in abundance upon Hy treatment were found. Five of these polypeptides were identified by peptide mass fingerprinting, including Annexin 2 (ANX2), hnRNP A3 and Ubiquitin. Evidence obtained by Western blot analysis indicates that ANX2 is present in the nucleus and has its subcellular localization modulated by GC-treatment of ST1 cells. Our findings indicate complementary mechanisms contributing to the regulation of gene expression associated with ST1 cells' response to GCs.
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PMID:Differential proteomic analysis of the anti-proliferative effect of glucocorticoid hormones in ST1 rat glioma cells. 1712 50

Upon searching for glucocorticoid-regulated cDNA sequences associated with the transformed to normal phenotypic reversion of C6/ST1 rat glioma cells, we identified Nrp/b (nuclear restrict protein in brain) as a novel rat gene. Here we report on the identification and functional characterization of the complete sequence encoding the rat NRP/B protein. The cloned cDNA presented a 1767 nucleotides open-reading frame encoding a 589 amino acids residues sequence containing a BTB/POZ (broad complex Tramtrack bric-a-brac/Pox virus and zinc finger) domain in its N-terminal region and kelch motifs in its C-terminal region. Sequence analysis indicates that the rat Nrp/b displays a high level of identity with the equivalent gene orthologs from other organisms. Among rat tissues, Nrp/b expression is more pronounced in brain tissue. We show that overexpression of the Nrp/b cDNA in C6/ST1 cells suppresses anchorage independence in vitro and tumorigenicity in vivo, altering their malignant nature towards a more benign phenotype. Therefore, Nrp/b may be postulated as a novel tumor suppressor gene, with possible relevance for glioblastoma therapy.
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PMID:Overexpression of Nrp/b (nuclear restrict protein in brain) suppresses the malignant phenotype in the C6/ST1 glioma cell line. 1968 78

Hypoxia and necrosis are fundamental features of glioma, and their emergence is critical for the rapid biological progression of this fatal tumor. The presence of vaso-occlusive thrombus is higher in grade IV tumors [glioblastoma multiforme (GBM)] compared with lower grade tumors, suggesting that the procoagulant properties of the tumor contribute to its aggressive behavior, as well as the establishment of tumor hypoxia and necrosis. Tissue factor (TF), the primary cellular initiator of coagulation, is overexpressed in GBMs and likely favors a thrombotic microenvironment. Phosphatase and tensin homolog (PTEN) loss and hypoxia are two common alterations observed in glioma that may be responsible for TF upregulation. In the present study, ST1 and P7 rat glioma lines, with different levels of aggressiveness, were comparatively analyzed with the aim of identifying differences in procoagulant mechanisms. The results indicated that P7 cells display potent procoagulant activity compared with ST1 cells. Flow cytometric analysis showed less pronounced levels of TF in ST1 cells compared with P7 cells. Notably, P7 cells supported factor X (FX) activation via factor VIIa, whereas no significant FXa generation was observed in ST1 cells. Furthermore, the exposure of phosphatidylserine on the surface of P7 and ST1 cells was investigated. The results supported the assembly of prothrombinase complexes, accounting for the production of thrombin. Furthermore, reverse transcription-quantitative polymerase chain reaction showed that CoCl2 (known to induce a hypoxic-like stress) led to an upregulation of TF levels in P7 and ST1 cells. Therefore, increased TF expression in P7 cells was accompanied by increased TF procoagulant activity. In addition, hypoxia increased the shedding of procoagulant TF-bearing microvesicles in both cell lines. Finally, hypoxic stress induced by treatment with CoCl2 upregulated the expression of the PAR1 receptor in both P7 and ST1 cells. In addition to PAR1, P7, but not ST1 cells, expressed higher levels of PAR2 under hypoxic stress. Thus, modulating these molecular interactions may provide additional insights for the development of more efficient therapeutic strategies against aggressive glioma.
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PMID:Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model. 2734 44


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