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)

Functional data for the promoter of the beta 1-adrenergic receptor (beta 1AR) gene are lacking. We previously cloned the ovine beta 1AR gene and mapped the transcription start sites. We now report data on ovine beta 1AR gene expression obtained by transient transfection. Progressive deletion of upstream 5' flanking region moderately increased transcription activity in three cell lines compared to the full-length promoter. Deletion of sequences between -1530 and -953 produced the greatest increase in transcriptional activity. This region encompassed a putative GRE and an AP1 site. Deletion of the transcription start sites eliminated nearly all of the activity. Dexamethasone significantly increased activity of each of the promoter constructs tested in C6 glioma cells and an embryonic myocardial cell line, W1 cells. T3 alone had no effect and cotreatment with T3 did not augment the effects of dexamethasone. We conclude, basal transcription activity is repressed by a mechanism which operates through element(s) in the proximal promoter. Glucocorticoids increase transcription through mechanism(s) within the same region. We speculate that this region in the ovine beta 1AR promoter may be responsible for its unique transcription regulation.
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PMID:Functional analysis of the 5' flanking sequence in the ovine beta 1-adrenergic receptor gene. 748 98

Phospholipase C-beta 1 (PLC-beta 1) exists as two immunologically indistinguishable polypeptides of 150 and 140 kDa and is encoded in rat brain by two distinct transcripts of 5.4 and 7.2 kilobases (kb). cDNA corresponding to the entire 5.4-kb transcript as reported previously reveals an open reading frame that is capable of coding a 1216-amino acid polypeptide (Suh, P. G., Ryu, S. H., Moon, K. H., Suh, H. W., and Rhee, S. G. (1988) Cell 54, 161-169). We have now isolated cDNAs corresponding to the entire 7.2-kb transcript from a rat brain cDNA library. The 7.2-kb transcript differs from the previously reported 5.4-kb transcript by possessing both an additional 118 nucleotides located near the end of the coding sequence and a 1738-nucleotide extension of the 3'-flanking region. The presence of the 118-nucleotide insert in the cumulative 7.2-kb sequence gives rise to an open reading frame that is capable of coding a 1173-amino acid polypeptide (PLC-beta 1b), the carboxyl-terminal sequence of which differs from that of the 1216-amino acid polypeptide (PLC-beta 1a) derived from the 5.4-kb transcript. Antibodies were raised against synthetic peptides corresponding to the carboxyl-terminal portions of PLC-beta 1a and PLC-beta 1b. Immunoblot analysis with these isozyme-specific antibodies revealed that both PLC-beta 1a and PLC-beta 1b are expressed in rat brain and C6Bu-1 glioma cells and that PLC-beta 1a and PLC-beta 1b correspond to the previously identified 150- and 140-kDa PLC-beta 1 enzymes, respectively. Analysis of PLC-beta 1 genomic DNA indicates that PLC-beta 1a and PLC-beta 1b are derived from a single gene by alternative RNA splicing.
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PMID:Two forms of phospholipase C-beta 1 generated by alternative splicing. 751 Jun 82

To analyze the process of mesenchymal differentiation in vitro, we examined 5 human glioblastomas as biopsy specimens, monolayer cultures and 3-dimensional fragment spheroid cultures for the immunohistochemical expression of extracellular matrix (ECM) components (collagen types I, III-VI, laminin) and integrin receptors (beta 1, beta 2, beta 3 and beta 4 chains). mRNA for type-I and type-IV collagen alpha I chains was quantified using reverse transcription-polymerase chain reaction. In situ, glioma cells expressed beta 1, the common beta chain of most integrin ECM receptors, while ECM components were restricted to vascular elements. Early monolayer cultures showed a marked increase in ECM components (interstitial collagens more than basement membrane components), and coexpression of ECM components and glial fibrillary acidic protein (GFAP) by most cells. beta 2 and beta 3 integrins were upregulated in the primary cultures. In the fifth passages, GFAP-positive cells were decreased and collagen-expressing cells increased. The spheroids exhibited preserved GFAP staining, neoexpression of beta 4 integrin in some tumors, and variable ECM expression by glioma cells which was lower than that in monolayer cultures. ECM deposition usually commenced in central spheroid areas where the Ki-67 proliferation index was low. We conclude that different culture systems are characterized by distinct expression patterns for ECM components and receptors, and that mesenchymal features in cultured gliomas arise due to transdifferentiation of glioma cells.
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PMID:Collagens, integrins and the mesenchymal drift in glioblastomas: a comparison of biopsy specimens, spheroid and early monolayer cultures. 752 12

Utilizing a human astrocyte-derived glioma cell line, we have demonstrated the presence of a vitronectin receptor, alpha v beta 3, and a fibronectin receptor, alpha 5 beta 1, on the surface of the cells spreading on the respective adhesion molecules by immunohistochemical analyses. By phase-contrast microscopy, these receptors were found to be expressed predominantly in the focal contact-like area, suggesting that they were involved in the spreading of the cells upon contact with these adhesion molecules. Interestingly, they appeared to have differential functions and roles as integrins as evidenced by different time-dependent distribution profiles on the cell surface in the serum-containing medium. Furthermore, both vitronectin and fibronectin seem to have chemotactic effects onto the glioma cells as observed in a Boyden chamber study. Although these receptors are not expected to be present on the surface of astrocytes under physiological conditions, they may be expressed thereon and involved in gliosis when the cerebral vasculature is traumatized and, thereby, blood proteins, including vitronectin and fibronectin, come into contact with the astrocytes.
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PMID:Localization of vitronectin- and fibronectin-receptors on cultured human glioma cells. 752 46

The gene expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was studied in human gliomas in vivo and in vitro to evaluate their roles in glioma invasion. Simultaneous expression of one to four MMP genes and two TIMP genes was found in 17 surgical glioma specimens, and one MMP (gelatinase A) gene and two TIMP genes were simultaneously expressed in tissue of three brains. The concomitant overexpression of gelatinase A, gelatinase B, and occasional matrilysin genes was associated with the malignancy of gliomas and accompanied by overexpression of the TIMP-1 gene. In five human glioma cell lines, gelatinase A, TIMP-1, and TIMP-2 genes were constitutively expressed in alll cell lines: the matrilysin gene in three cell lines; the stromelysin gene in two cell lines; and the interstitial collagenase gene in one cell line. There was a clear difference in the expression of gelatinase B and stromelysin genes between surgical glioma specimens and glioma cell lines: the gelatinase B gene was not expressed constitutively in vitro but was overexpressed in vivo, whereas the stromelysin gene was not expressed in vivo but was expressed in some cell lines. To find the cause of that difference in vivo and in vitro, the transcriptional regulations of MMP and TIMP genes by tumor promoter, growth factors, or cytokines were studied in vitro. Interstitial collagenase, gelatinase B, stromelysin, and TIMP-1 genes were upregulated in many cell lines by phorbol-12-myristate-13-acetate (PMA) and in some cell lines by epidermal growth factor, tumor necrosis factor-alpha, or interleukin-1 beta. Transforming growth factor-beta 1 (TGF beta 1) upregulated gelatinase A and matrilysin genes in some cell lines, and there were no clear responses from any MMP and TIMP genes to interleukin-6. Thus, the transcriptional modulation of MMP genes by these growth factors and cytokines seemed insufficient to explain the difference in gelatinase B and stromelysin gene expressions in vivo and in vitro and was suggestive of the genetic alteration of glioma cells in vitro, the heterogeneous cell population in glioma tissues, or both. Furthermore, the in vitro invasion of glioma cells through Matrigel in response to PMA, TGF beta 1, or TIMP-1 was assessed by chemoinvasion assay. In most cell lines, invasion was significantly stimulated by PMA or TGF beta 1 but suppressed by TIMP-1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. 761 76

The authors investigated the effects of a nontoxic differentiation inducer, phenylacetate (PA), on neuroectodermal tumor-derived cell lines. Treatment of medulloblastoma (Daoy and D283 MED) and glioma (U-251MG, C6, and RG2) cell lines resulted in a dose-dependent decline in DNA synthesis and cell proliferation, associated with accumulation in the G0/G1 phase of the cell cycle. Phenylacetate decreased transforming growth factor (TGF)-beta 2 production by medulloblastoma Daoy cells. Neutralizing antibodies against either TGF beta 2 or TGF beta 1 failed to block the growth arrest observed. This suggests that, unlike other differentiation agents, such as retinoic acid, the effect of PA on medulloblastoma proliferation is not mediated by a TGF beta pathway. In addition to cytostasis, PA induced marked morphological changes in U-251MG and C6 glioma cells associated with increased abundance of glial fibrillary acidic protein-positive processes. Although the morphology of PA-treated medulloblastoma cells was not significantly altered, the D283 MED cells exhibited increased expression of neurofilament proteins and Hu antigen, indicative of differentiation along a neuronal pathway. The effects of PA on the medulloblastoma cell lines were compared to its effects on the human neuroblastoma cell line BE(2)C, which is capable of a bidirectional differentiation toward a neuronal or a glial/schwann cell pathway. In BE(2)C cells, PA induced differentiation toward a schwann/glial cell-like phenotype, suggesting that the choice of differentiation pathway is cell type and agent specific. These in vitro antiproliferative and differentiation inducing effects of PA suggest that this agent warrants further evaluation as a potential therapeutic modality for the treatment of medulloblastoma and malignant glioma in humans.
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PMID:Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate. 767 18

To identify potential cell surface receptors for chicken cytotactin (CT), we have characterized the ability of recombinant fusion proteins spanning the proximal fibronectin (FN) type III repeats of the molecule to support attachment of glioma and carcinoma cell lines. The third FN type III repeat, which contains the RGD tripeptide, supported cell attachment and cell spreading; however, mutation of RGD to RAD did not result in significant loss of either activity. In addition, the same repeat of mouse CT, which contains a natural mutant, RVD, also supported cell attachment and spreading, although at a lower level; both activities were increased by mutation of the RVD sequence to RGD. Studies utilizing RGD-containing peptides and well-characterized antibodies to integrins indicated that cell attachment to the third FN type III repeat was mediated by at least two different integrin receptors of the alpha v subtype. Additional cellular receptors may also be involved in cell attachment to CT. For example, an antibody to the beta 1 subfamily of integrins partially inhibited binding of cells to intact CT but did not inhibit cell binding to the third FN type III repeat. These findings suggest that the RGD site in CT is able to mediate cell attachment to integrins and thus is not a cryptic adhesion site. They also open the possibility that the functions of CT in processes such as counteradhesion, cell migration, cell proliferation, and cell differentiation may be mediated in part by interaction with multiple integrins.
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PMID:Multiple integrins mediate cell attachment to cytotactin/tenascin. 769 84

Chromatin condensation during apoptosis induced by TGF beta 1 in T24 glioma and 476-16 trigeminal neurinoma (Schwannoma) cells was examined and compared with that occurring during mitosis. Apoptotic (round-up) cells were selectively detached from the culture surface by a mechanical shock. Their histones were analysed in comparison with those obtained from TGF beta 1-treated cells remaining attached to the culture surface, from control cells not treated with TGF beta 1 and from metaphase cells. While mitosis-specific hyperphosphorylation of histones H1 and phosphorylation of histone H3 was not observed in apoptotic cells, apoptotic chromatin lacked ubiquitinated histone H2A (histone uH2A) as did metaphase chromosomes. The cellular level of free ubiquitin and the overall pattern of ubiquitin-conjugated proteins were, however, found to remain unaltered in apoptotic cells, suggesting that the ubiquitin conjugating machinery for histone H2A may be specifically perturbed during the chromatin condensation occurring in apoptosis.
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PMID:Disappearance of ubiquitinated histone H2A during chromatin condensation in TGF beta 1-induced apoptosis. 776 93

To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains.
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PMID:N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 776 44

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


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