Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A long-term cell culture of human glioblastoma was investigated microscopically, virologically, and biochemically. Reverse transcriptase activity was detected in cultured human glioblastoma cells. 3H uridine was incorporated into particles of buoyant density at 1.07 g/ml (Ficoll) which is equal to that of Oncorna virus particles, but 3H thymidine was not incorporated at all. Furthermore, reverse transcriptase activity was also demonstrated with the particles, suggesting that the cultured human glioblastoma cells were producing type C Oncorna virus. Ultrastructural observations of cell culture of glioblastoma showed type C virus particles in cisternae and culture medium. Budding of the virus was also seen on the surface of the cell. The mean diameter of the particles was approximately 100 nm. Ca. 1.1 nm of spikes protruded from the envelope. Both types of virions were observed, i.e. the doughnut-shaped type form and the solid circular form.
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PMID:Type C particles in culture of human glioblastoma cells. 8 68

The growth of a panel of 22 different human tumor, leukemia, and lymphoma cell lines was examined in a human tumor cloning assay in agar or methylcellulose and a tritiated thymidine uptake assay. The cultures were performed in the absence or presence of increasing concentrations (0.5-500 ng/ml) of nerve growth factor (NGF). The growth of 17 of the 22 cell lines was not significantly and reproducibly affected by NGF. There was minor (1.2-fold) but reproducible stimulation of clonal growth in one glioblastoma cell line (86-HG-39) by NGF, but in this cell line NGF induced no growth modulation in a tritiated thymidine uptake assay. However, clonal growth of another glioblastoma cell line (87-HG-31) and all three lung cancer cell lines tested (HTB 119, HTB 120, CCL 185) could be stimulated up to 3-fold by NGF with a dose-response relationship for the growth factor. Growth stimulation by NGF could be completely reversed by neutralizing anti-NGF antibody and by the tyrosine kinase inhibitor genistein. Evaluation of secondary plating efficiency revealed the stimulation of colony formation as representing self-renewal and not terminal differentiation. Reverse transcriptase-PCR experiments in the five responding cell lines showed expression of both low-affinity NGF receptor (glycoprotein 75) and c-trk transcripts on the mRNA level. Of the five responding cell lines, only 86-HG-39, the cell line with the lowest responsiveness, revealed low-affinity NGF receptor on the protein level; the other four cell lines with high responsiveness, including the three lung cancer cell lines, expressed no low-affinity NGF receptor as shown by fluorescence-activated cell sorter analysis and immunoprecipitation using the ME 20.4 antibody. Immunoprecipitation using anti-trk antibodies was negative in all five responding cell lines. However, binding studies with iodinated NGF showed only low-affinity binding on the 86-HG-39 cell line and only high-affinity binding on the high-responder cell lines CCL 185 and 87-HG-31. In summary, our data suggest that NGF can be operative in stimulation of clonal growth of malignant tumor cells. High-affinity but not low-affinity binding sites mediate signal transduction for clonal growth and signaling involves tyrosine kinase activity.
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PMID:Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling. 753 48

Three new cell lines of human glioblastoma have been established. These cells co-expressed hepatocyte growth factor (HGF) and its receptor, c-Met, genes in vitro. Reverse-transcriptase/polymerase-chain reaction study revealed that the cells also expressed gene for HGF activator, a recently cloned serine proteinase, suggesting that HGF might have a role in glioma cells in vitro as an autocrine factor. The activator mRNA was also detected in other well-established glioma cell lines, glioma tissues and normal brain. The concomitant expression of HGF, HGF activator and c-met was also detected in one glioblastoma case in vivo out of five tested.
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PMID:Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. 755 48

The expression of facilitative glucose transporter (GLUT) isoforms in human astrocytic tumors was examined. Reverse transcriptase-polymerase chain reaction of a surgically biopsied glioblastoma was carried out using the degenerative oligonucleotide primers corresponding to the sequences of the human facilitative glucose transporter family, and polymerase chain reaction products were hybridized with human GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5 cDNA probes. The results showed that a biopsied glioblastoma expressed GLUT1, GLUT3, and GLUT4 glucose transporter genes. Northern blot analysis of total RNA (10 micrograms) from a biopsied glioblastoma showed the transcripts of only GLUT1 and GLUT3, suggesting that the expression of insulin-responsive glucose transporter GLUT4 mRNA is relatively low. Immunoblot analysis of biopsied glioblastoma tissues by polyclonal antibodies against the C-terminal synthetic peptides of GLUT1, GLUT3, and GLUT4 showed a single band of each polypeptide. However, elevated expression of GLUT1 and GLUT3 glucose transporters was not observed in the glioblastoma. Astrocytic tumor tissues (n = 14) were also examined immunohistochemically. Reactive products for GLUT1 were observed in the luminal surface of capillaries in all cases, whereas tumor cells were positive for GLUT1 in only two of 14 cases. GLUT3 was positive in astrocytic tumor cells in all cases. Three of 14 cases expressed the GLUT4 protein, which was localized in the cytoplasm of tumor cells. These results suggest that the facilitative glucose transport may be altered in astrocytic tumor cells and thus display a significant change in glucose metabolism.
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PMID:Expression of facilitative glucose transporter isoforms in human brain tumors. 824 60

Fas/APO-1 (CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. We previously reported that Fas expression is predominantly induced in perinecrotic glioma cells, suggesting that Fas induction is associated with apoptosis and necrosis formation, a histological hallmark of glioblastomas. In this study, we assessed the expression of FasL in 10 glioblastoma cell lines and in 14 astrocytic brain tumors (three low-grade astrocytomas and 11 glioblastomas). Reverse transcriptase (RT)-PCR revealed that all glioblastoma cell lines and primary astrocytic brain tumors express FasL. Immunohistochemically, FasL was predominantly expressed on the plasma membrane of glioma cells. These results suggest that FasL expression is common in human astrocytic brain tumors and may cause apoptosis of glioma cells if Fas expression is induced.
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PMID:Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. 921 71

Recently, there have been several reports describing the cloning and characterization of the novel family of protein tyrosine phosphatase-like receptor molecules (known as IA-2 and PTP-NP/PTP-IAR/IA-2beta/phogrin), which may act as autoantigens in diabetes. Here, we report the molecular characterization and chromosomal localization of a new isoform of this family in brain termed PTP-NP-2 (for PTP-NP tyrosine phosphatase isoform), and its function in rat primary hippocampal neurons. PTP-NP-2 has 48% identity to IA-2. The principal difference between PTP-NP-2 and PTP-NP is a 17-amino-acid insert near the N-terminus of PTP-NP that is absent in PTP-NP-2. Genomic DNA analysis indicates that the 17-amino-acid insert is coded by a separate exon, suggesting that both IA-2beta and PTP-NP-2 are isoforms arising by alternate splicing of the same gene. Reverse transcriptase-PCR revealed that both isoforms are present in human SH-SY5Y neuroblastoma cells. PTP-NP-2 mRNA expression is highly restricted, with a 5.5-kb specific transcript in human fetal and adult brain and 5.5 and 3. 8 kb in human adult pancreas. SH-SY5Y neuroblastoma and U87-MG glioblastoma cells showed specific transcripts of 5.5 and 3.8<HSP SP = "0.25">kb, respectively, indicating the existence of several isoforms of this molecule in the nervous system. The human gene encoding PTP-NP-2 was assigned to human chromosome 7q22-qter using Southern blot analysis of genomic DNAs from rodent/human somatic hybrid cell lines. Confocal microscopy analyses of rat primary hippocampal neurons revealed that PTP-NP-2 is abundantly expressed on synaptic boutons in primary neurons. Wild-type PTP-NP-2 showed no measurable tyrosine phosphatase activity using an in-vitro pNPP assay. Examination of the PTP-NP-2 catalytic consensus sequence revealed that this sequence differed from the typical tyrosine phosphatase-domain consensus sequence by an alanine to aspartate change (amino acid 930). Mutation of aspartate 930 to alanine produced a catalytically active enzyme, suggesting that native PTP-NP and its isoform PTP-NP-2 are catalytically inactive receptor protein tyrosine phosphatase homologues. Taken together, these results indicate that the tyrosine phosphatase PTP-NP-2 is a new isoform of PTP-NP tyrosine phosphatase, is expressed on synaptic boutons and may participate in the regulation of synaptic bouton endocytosis.
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PMID:Characterization and chromosomal localization of PTP-NP-2, a new isoform of protein tyrosine phosphatase-like receptor, expressed on synaptic boutons. 971 34

Voltage-gated K(+) channels (Kv1) are important in glia, being required for cell proliferation. Herein, reactive astrocytes from a rat cerebellar lesion were shown to contain Kv1.1, -1.2, -1.3, -1.4, and -1.6 alpha plus beta1.1 subunits, as well as an unusual beta2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and beta1.1 subunits. Reverse transcriptase-polymerase chain reaction revealed a novel product of the beta2 gene in C6 cells and reactive astrocytes, but not in cultured astrocytes or rat normal brain. Its cloning identified a variant, Kvbeta2.1A, alternatively spliced between I24 and Y39. Despite this 14 residue deletion, Kvbeta2.1A assembled cotranslationally with Kv1.1 or -1.2 and, when coexpressed with Kv1. 4 in oocytes, increased the inactivation rate of this K(+) current. Whereas the full-length beta2.1 gave a large increase in the amplitude of the Kv1.1 current in oocytes, the effect of beta2.1A varied from a modest elevation of the current to a slight suppression in some cases. In summary, this is the first report of the existence of an alternatively spliced product of the Kvbeta2.1 gene in C6 cells and reactive astrocytes, and supports the involvement of its core region (residues 39 onward) in assembly with alpha subunits while excluding a contribution of the adjacent 14 residues to accelerating the inactivation of Kv1.4.
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PMID:A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum. 1060 34

Evidence has accumulated showing that vasoactive peptides, such as endothelin-1, adrenomedullin and urotensin-II, are expressed in various kinds of tumour cells. In the present study, the expression of endothelin-1 and endothelin receptors was studied in eight human tumour cell lines: T98G (glioblastoma), IMR-32 and NB69 (neuroblastoma), BeWo (choriocarcinoma), SW-13 (adrenocortical carcinoma), DLD-1 (colonic carcinoma), HeLa (cervical carcinoma) and VMRC-RCW (renal carcinoma). Reverse transcriptase-PCR showed expression of endothelin-1 mRNA in seven out of the eight cell lines, the exception being BeWo cells. ET(A) receptor mRNA was expressed in T98G, IMR-32 and NB69 cells, but weakly in the other cells. ET(B) receptor mRNA was expressed in IMR-32, NB69 and BeWo cells, but only weakly in T98G and HeLa cells. Immunoreactive endothelin was detected in the culture media of six out of the eight cell lines, but not in that of IMR-32 or BeWo cells. Treatment of T98G cells with an anti-endothelin-1 antibody or an anti-adrenomedullin antibody for 24 h decreased cell numbers to approx. 84% and 90% of control respectively. Treatment with the ET(A) receptor antagonist BQ-610 (1 microM) significantly decreased cell number to about 90% of control, whereas the ET(B) receptor antagonist BQ-788 had no significant effect. On the other hand, exogenously added endothelin-1, adrenomedullin or urotensin-II (0.1 microM) had no significant effects on cell number. These results suggest that endothelin-1 acts as a paracrine or autocrine growth stimulator in tumours. The effect of endothelin-1 on tumour growth appears to be mediated by the ET(A) receptor.
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PMID:Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation. 1219 50

Our laboratory demonstrated that endoplasmic reticulum iPLA2 (ER-iPLA2) activity protects renal cells from oxidant-induced cell death and lipid peroxidation. The goals of this study were to determine the PLA2 isoform(s) responsible for ER-iPLA2 activity in different species and tissues. ER-iPLA2 activity was observed in microsomes from rabbit and rat kidney, heart, and brain as well as in human kidney (Caki-1 and HEK293) and glioblastoma (A172) cell lines. Reverse transcriptase-polymerase chain reaction results demonstrated the presence of iPLA2gamma (group VIB PLA2) message in all tissues tested. Immunoblot analysis and PLA2 inhibitor studies with methyl arachidonyl fluorophosphonate and enantiomers of bromoenol lactone demonstrated that the ER-iPLA2 in rabbit kidney and heart and rat kidney is iPLA2gamma. These results demonstrate the expression of ER-iPLA2gamma (group VIB) across species and tissues, and suggest that iPLA2gamma may play critical roles in oxidant-induced cell injury.
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PMID:Identification and distribution of endoplasmic reticulum iPLA2. 1562 60

Gliomas, particularly glioblastoma multiforme, perturb the blood-brain barrier and cause brain edema that contributes to morbidity and mortality. The mechanisms underlying this vasogenic edema are poorly understood. We examined the effects of cocultured primary cultured human glioblastoma cells and glioma-derived growth factors on the endothelial cell tight junction proteins claudin 1, claudin 5, occludin, and zonula occludens 1 of brain-derived microvascular endothelial cells and a human umbilical vein endothelial cell line. Cocultured glioblastoma cells and glioma-derived factors (e.g. transforming growth factor beta2) enhanced the paracellular flux of endothelial cell monolayers in conjunction with downregulation of the tight junction proteins. Neutralizing anti-transforming growth factor beta2 antibodies partially restored the barrier properties in this in vitro blood-brain barrier model. The involvement of endothelial cell-derived matrix metalloproteinases (MMPs) was demonstrated by quantitative reverse-transcriptase-polymerase chain reaction analysis and by the determination of MMP activities via zymography and fluorometry in the presence or absence of the MMP inhibitor GM6001. Occludin, claudin 1, and claudin 5 were expressed in microvascular endothelial cells in nonneoplastic brain samples but were significantly reduced in anaplastic astrocytoma and glioblastoma samples. Taken together, these in vitro and in vivo results indicate that glioma-derived factors may induce MMPs and downregulate endothelial tight junction protein and, thus, play a key role in glioma-induced impairment of the blood-brain barrier.
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PMID:Endothelial cell barrier impairment induced by glioblastomas and transforming growth factor beta2 involves matrix metalloproteinases and tight junction proteins. 1843 Dec 53


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