Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT) is expressed at a low level in many cells. As is the case with several other "housekeeping genes," thorough studies of hprt gene regulation have been hampered by the low levels of its mRNA. We have used RNA/RNA hybridization in solution to determine the concentration of hprt-RNA in human cells. The sensitivity and specificity of the method have been validated, and it is shown that hprt-RNA can be accurately determined at a level of a few mRNA molecules per cell. As expected for a housekeeping gene, low and relatively constant hprt-RNA levels (0.3-0.8 pg/micrograms DNA) were found in primary cultures of normal amnion cells and fibroblasts, EBV-transformed lymphoblastoid cell lines, neuroblastoma, glioblastoma, and melanoma cell cultures. While resting lymphocytes were found to contain very low amounts of hprt-RNA, lymphocytes stimulated with phytohemagglutinin (PHA) showed a 10-fold increase to about 0.8-1.2 pg/microgram DNA, which corresponds to 6-10 hprt-RNA molecules per cell. The level started to increase about 20 h after PHA stimulation, 5-10 h before the onset of DNA synthesis, and a steady-state level was reached after 2-3 days in culture. In PHA-stimulated lymphocytes from two brothers with inherited HPRT deficiency (Lesch-Nyhans syndrome), the hprt-RNA level in PHA-stimulated lymphocytes was only about 25% of that in normal subjects. In T-cells selected for HPRT deficiency by growth in 6-thioguanine medium, the levels of hprt-RNA were either normal or very low, which probably reflects the different nature of the mutations involved. These results demonstrate the sensitivity of this method for determinations of low levels of RNA and clearly show induction of hprt-RNA after mitogenic stimulation of human lymphocytes.
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PMID:Levels of hypoxanthine phosphoribosyltransferase RNA in human cells. 168 3

The 'octamer' sequence, ATGCAAAT or its complement ATTTGCAT, is a key element for the transcriptional regulation of immunoglobulin genes in B-lymphocytes as well as a number of housekeeping genes in all cell types. In lymphocytes, the octamer-binding protein Oct-2A and variants thereof are thought to contribute to the B-cell specific gene expression, while the ubiquitous protein Oct-1 seems to control general octamer site-dependent transcription. Various other genes, for example interleukin-1 and MHC class II genes, contain an octamer sequence in the promoter and are expressed in cells of both the immune and nervous systems. This prompted us to analyze the octamer-binding proteins in the latter cells. Using the electrophoretic mobility shift assay, at least six novel octamer binding proteins were detected in nuclear extracts of cultured mouse astrocytes. These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines. The nervous system-derived (N-Oct) proteins bound to the octamer DNA sequence in a manner which is indistinguishable from the Oct-1 and Oct-2A proteins. The relationship of the N-Oct proteins to Oct-1 and Oct-2A was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant Oct-1 and Oct-2A proteins. On the basis of these assays, all N-Oct-factors were found to be distinct from the ubiquitous Oct-1 and the lymphoid-specific Oct-2A proteins. In melanoma cells that contain the N-Oct-3 factor, a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an Oct-2A expression vector. We therefore speculate that N-Oct-3 and other N-Oct factors have a specific role in gene expression in cells of the nervous system.
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PMID:Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. 221 22

Acid beta-glucosidase (beta Glc) is a housekeeping enzyme whose expression is ubiquitous, but differs greatly according to tissue of origin. Expression of a reporter gene under the control of a 622 bp fragment of the beta Glc promoter correlated roughly with the relative amount of beta Glc mRNA detected in five different cell lines, suggesting that elements within this region play a role in determining differential expression of the beta Glc gene. Experiments using deletion mutants revealed that differential expression of beta Glc is not due to the presence of promoter elements that are active in only certain cell types, but rather due to subtle changes in the magnitude of the effect of the different elements. Strikingly, regulatory elements located upstream of the TATA box are dispensible in several cell types, whereas elements located within exon 1 of the beta Glc gene are essential for reporter gene expression in cultured cells. At least two exon 1 elements regulate mRNA levels, and one double stranded probe containing exon 1 sequences binds a factor present in extracts from HeLa and glioblastoma cells. Additionally, at least two of the exon 1 elements act in an orientation-independent fashion. Thus, it is likely that at least a subset of the exon 1 elements act as transcriptional enhancers.
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PMID:Regulation of the human acid beta-glucosidase promoter in multiple cell types. 789 61

Acid beta-glucosidase (beta Glc) activity and mRNA levels were measured in several human cell lines, and found to vary over 50-fold. A comparison between relative levels of beta Glc enzyme and mRNA levels revealed three patterns. The first group, including epithelial, lymphoblast, histiocyte, glioblastoma and astrocytoma cell lines, showed a direct relationship between relative levels of mRNA and enzyme activity, indicating that mRNA levels play an important role in determining enzyme activity. The second group, including fibroblast, promyelocyte and neuroglioma cell lines, also showed a direct relationship between beta Glc enzyme and mRNA levels within this group, but had enzyme activities that were approximately sixfold higher than expected, when compared with enzymes within the first group. The third pattern was exhibited by a single monocyte cell line, which showed high levels of beta Glc mRNA, but only intermediate levels of enzyme activity. These results suggest that although beta Glc mRNA levels play a major role in regulating beta Glc activity, other mechanisms also influence enzyme levels in certain cell lines. These results also demonstrate the importance of examining several different cell types when considering mechanisms of housekeeping gene regulation. Additionally, culturing cells in the presence of the beta Glc-specific inhibitor, conduritol-B-epoxide, did not affect beta Glc mRNA levels, and cells derived from normals had levels of beta Glc mRNA comparable to those from Gaucher disease patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of expression of the gene encoding human acid beta-glucosidase in different cell types. 850 Jul 68

Retinoic acid (RA) has been used to induce the regression of refractory T-cell lymphoma. In vitro and in vivo studies have shown that RA exerts this effect through the induction of apoptosis. This study was designed to investigate the molecular pathway of RA-induced apoptosis in T-lymphoma cell lines.RA-induced apoptosis was verified by morphology, flow cytometry, and DNA ladder analysis. Differential display method using a combination of 12 poly(A)-anchored primers and 20 arbitrary primers was adopted for gene cloning. Total RNAs were extracted from H9 cell line at 0, 6, 12, and 24 hours after All-trans RA (ATRA) treatment and the serial expression patterns of the candidate fragments were recognized. The cloned gene fragments were then analyzed and confirmed by Northern blot analysis on H9 and SR786 cell lines.ATRA-induced apoptosis of T-cell lymphoma was protein synthesis-dependent. The execution or irreversible phase of apoptosis appeared to occur at 6-12 hours of RA treatment. Among the 60,000 arbitrarily displayed bands, 25 of 250 candidate fragments were selected for further cloning and sequencing. A total of 14 clones could be matched to known genes and were categorized into four groups: A) transcription factors: prothymosin, CA150, p78 serine/threonine kinase, IL-1beta-stimulating gene, glucocorticoid receptor, MLN64/CAB1, gastrin-binding protein, and polypeptide from glioblastoma; B) chaperone: 90 kDa heat shock protein; C) ion channel: chloride channel protein 3; and D) cytoskeleton: cytovillin2/ezrin and vimentin. Another two clones of genes were of unrecognized functions. The remaining 11 clones belonged to unmatched or novel genes. The expression of these genes varied, either upregulated or downregulated, in response to ATRA treatment.RA-induced apoptosis may involve a cascade of genes that are related to transcription regulation, stress response, housekeeping, and the execution of apoptosis. The clarification of the RA-induced apoptotic pathway will help us to understand the molecular mechanism of cancer differentiation agents.
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PMID:Retinoic acid-induced apoptotic pathway in T-cell lymphoma: Identification of four groups of genes with differential biological functions. 1114 66

Although scientific advances have recognised the prognostic power of telomerase activity in different cancers, as yet there has been no investigation regarding the expression variation of telomerase subunits in glioma tissues and cell lines. In this study, a recurrent anaplastic ependymoma and seven glioblastoma biopsy samples, four cell lines and four controls including two normal brain tissues were analysed for telomerase subunit expression profiles together with telomerase activity. Since telomerase activity is linked to tumourgenesis, the genes were analysed with respect to their expression variation. TEP1 was expressed in all glioma cell lines and 70% of glioblastoma tissues, in addition to the control brain tissues. Tankyrase was expressed in 85% of the glioblastoma tissues and was down-regulated in the recurrent anaplastic ependymoma tissue control cell lines. However, it was expressed in the control tissues. Dyskerin was expressed in all cell lines and tissues apart from U87-MG and NHA cells and the recurrent anaplastic ependymoma tissue. As expected, PARP1 and GAPDH showed constitutive expression throughout all cell lines and tissues since both are known to be housekeeping genes. hTERT was expressed in all glioma cell lines and tissues but was absent in the control cells and tissues. Telomerase activity was absent in IPDDC-A2 cells and 57% of the glioblastoma tissues. These results suggest that hTERT expression and not telomerase activity possibly represents a simple and reliable biological diagnostic tool.
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PMID:Telomerase subunits expression variation between biopsy samples and cell lines derived from malignant glioma. 1719 47

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. L2-miRNAs derived from the 3' end of the L2 consensus sequence and thus shared very similar sequences, indicating that L2-miRNAs could target transcripts with L2s in their 3'UTR. In line with this, many protein-coding genes carried fragments of L2-derived sequences in their 3'UTR: these sequences served as target sites for L2-miRNAs. L2-miRNAs and their targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. In addition, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells.
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PMID:LINE-2 transposable elements are a source of functional human microRNAs and target sites. 3086 25

Glioblastoma ( 'GBM' ) is the most aggressive type of primary malignant adult brain tumor, with very heterogeneous radio-graphic, histologic, and molecular profiles. A growing body of advanced computational analyses are conducted towards further understanding the biology and variation in glioblastoma. To address the intrinsic heterogeneity among different computational studies, reference standards have been established to facilitate both radiographic and molecular analyses, e.g., anatomical atlas for image registration and housekeeping genes, respectively. However, there is an apparent lack of reference standards in the domain of digital pathology, where each independent study uses an arbitrarily chosen slide from their evaluation dataset for normalization purposes. In this study, we introduce a novel stain normalization approach based on a composite reference slide comprised of information from a large population of anatomically annotated hematoxylin and eosin ( 'H&E' ) whole-slide images from the Ivy Glioblastoma Atlas Project ( 'IvyGAP' ). Two board-certified neuropathologists manually reviewed and selected annotations in 509 slides, according to the World Health Organization definitions. We computed summary statistics from each of these approved annotations and weighted them based on their percent contribution to overall slide ( 'PCOS' ), to form a global histogram and stain vectors. Quantitative evaluation of pre- and post-normalization stain density statistics for each annotated region with PCOS > 0.05% yielded a significant (largest p = 0.001, two-sided Wilcoxon rank sum test) reduction of its intensity variation for both 'H' & 'E' . Subject to further large-scale evaluation, our findings support the proposed approach as a potentially robust population-based reference for stain normalization.
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PMID:Towards Population-Based Histologic Stain Normalization of Glioblastoma. 3274 62

The aim of this study was to assess two protocols for their capacities to simultaneously isolate RNA, mtDNA and ncDNA from mammalian cells. We compared the Invitrogen TRIzol-based method and Qiagen DNeasy columns, using the HepG2 cell line and human primary glioblastoma stem cells. Both methods allowed the isolation of all three types of nucleic acids and provided similar yields in mtDNA. However, the yield in ncDNA was more than tenfold higher on columns, as observed for both cell types. Conversely, the TRIzol method proved more reproducible and was the method of choice for isolating RNA from glioblastoma cells, as demonstrated for the housekeeping genes RPLP0 and RPS9.
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PMID:Methods for simultaneous and quantitative isolation of mitochondrial DNA, nuclear DNA and RNA from mammalian cells. 3310 26