UMLS:C0027819 - FACTA Search

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

Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TRH is negatively regulated by T3 both in the hypothalamic paraventricular nucleus and transient transfection models. Mutations in hTR beta 1 genes are associated with the syndrome of generalized resistance to thyroid hormone. To investigate potential effects of mutant TRs on T3 regulation of the hTRH gene, transient gene expression assays were performed in human neuroblastoma (HTB-11) cells with an hTRH promoter-luciferase construct, wild type (WT) hTR beta 1, and three qualitatively distinct hTR beta 1 mutant forms (ED, OK and PV). In the presence of T3 (10(-9) M), liganded WT-hTR beta 1 inhibited hTRH promoter activity significantly (40%). Cotransfection of each of the two mutants (ED and OK) achieved similar levels of inhibition only at 10 to 100 fold increased T3 concentrations. Of interest, a 10x excess of mutant ED or OK could also exert dominant negative effects upon WT hTR beta 1-T3 mediated inhibitory actions on the hTRH promoter. In contrast, mutant TR-PV exerted neither inhibitory nor dominant negative effects at even higher concentrations of T3. Moreover, all three unliganded mutant forms stimulated TRH promoter activity significantly in the absence of T3, despite their different mutations in the ligand-binding domain (LBD). These data demonstrate that thyroid hormone resistance at the level of TRH gene regulation, due to reduced inhibitory actions of mutant TR-T3 complexes, as well as dominant negative effects upon WT hTR beta 1 mediated inhibition, likely contribute to elevated TSH values observed in the syndrome of thyroid hormone resistance.
...
PMID:Regulation of the human TRH (hTRH) gene by human thyroid hormone receptor beta 1 (hTR beta 1) mutants. 943 Aug 20

The mouse gene encoding ST8Sia IV/PST, one of two polysialic acid synthases, was isolated and characterized. The mST8Sia IV/PST gene was found to comprise over 60 kilobases and to be composed of five exons. Primer extension analysis revealed that transcription started from 333 nucleotides upstream of the translational initiation site. Transfection with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene revealed that the promoter activity of the -107/+145 region was correlated with the gene expression of mST8Sia IV/PST in embryonal carcinoma P19 and neuroblastoma F11 cells. This proximal promoter region lacks an apparent TATA box but has putative binding sites for transcription factors Sp1 and NF-Y (CCAAT binding protein) at nucleotide positions -66/-57 and -47/-37, respectively. Individual deletions and mutations of the inverted Sp1 binding site or inverted NF-Y binding site caused significant reduction of the promoter activity, indicating that each binding site was involved in essential transcription control. Mobility shift assaying also revealed that Sp1 and NF-Y in a nuclear extract of P19 cells bind to the promoter region of the mST8Sia IV/PST gene. Deletion of the region from -60 to -40, which contains parts of both the Sp1 and NF-Y binding sites, completely abolished the promoter activity, suggesting that both Sp1 and NF-Y are synergetically involved in transcription regulation of the mST8Sia IV/PST gene in P19 and F11 cells. Although the overall structures of the two polysialic acid synthase genes (ST8Sia II/STX and IV/PST) are very similar, there is no extensive sequence homology between the 5'-flanking regions of the ST8Sia II/STX and IV/PST genes, suggesting that these two genes are expressed under different regulatory systems.
...
PMID:Genomic structure and promoter activity of the mouse polysialic acid synthase (mST8Sia IV/PST) gene. 951 73

The expression of the neuropeptide galanin (GAL) is elevated in vivo upon nerve stimulation, injury, and in vitro by phorbol 12-myristate-13-acetate (PMA), suggesting that a signal pathway involving protein kinase C activation may be involved in GAL-gene activation. When plasmids containing a different length of the bovine GAL-promoter fused to luciferase were transfected into the human neuroblastoma cell line (SK-N-SH subclone SH-SY5Y), a PMA-responsive element was identified in the promoter-region -68 to -46 base pairs (bp). Co-transfection experiments with plasmids expressing cJun and cFos revealed that they could act alone, as well as synergistically with PMA to induce luciferase activity. Electrical mobility shift assays revealed that a cAMP response element (CRE)-like sequence (TGACGCGG; -59 to -52 bp) bound PMA-inducible nuclear proteins present in SH-SY5Y cells. These proteins appear to bind mainly as CRE-binding protein/activating-transcription-factor (CREB/ATF) and Jun/ATF heterodimers. In addition, an apparent PMA-inducible protein(s) not recognized by CREB/ATF and Jun antibodies bound to the CRE-like containing probe.
...
PMID:Characterization of phorbolester-inducible human neuronal factors involved in trans-activation of the galanin gene. 960 91

The neuronal promoter of human aromatic l-amino acid decarboxylase gene has been analysed to elucidate the mechanisms of neuron type-specific expression. The (-560/+92) promoter segment was sufficient to direct luciferase expression at a higher level in SK-N-BE neuroblastoma cells, than in CHP126 neuroepithelia, HepG2 hepatoma or SK-Hep1 epithelioma cells. Deletions experiments showed that this segment contained a neuronal-specific (element T1) and a SK-N-BE-specific (element N1) cis-activating sequences. Element T1 (-72/-36) bound Sp1 and NF-Y proteins, and unidentified neuronal-specific factors. Element N1 (-102/-72) bound cell-specific factors, identified as HNF-3, N-Oct-3/Brn-2 and N-Oct-2. HNF-3 proteins recognized the sequence TCAGTAAATA that matches the consensus motif. Oct-1, N-Oct-2 and N-Oct-3 bound the AAATAATGC sequence that overlaps the HNF-3 binding site. In addition, we show that the HNF-3 binding sites from aldolase C and HNF-3beta gene promoters also bind N-Oct-2 and N-Oct-3 proteins. These data suggest a functional interplay of winged helix/forkhead and POU-domain transcription factors on a variety of neuronal gene promoters.
...
PMID:Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3 bind overlapping sites on the neuronal promoter of human aromatic L-amino acid decarboxylase gene. 960 35

The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy.
...
PMID:Nuclear localization signal peptides enhance cationic liposome-mediated gene therapy. 960 6

Glioblastoma is one of the most malignant of all neoplasms, and often shows resistance to chemotherapy and radiation therapy. Ionizing radiation activates transcriptional factors, such as nuclear factor kappa-B (NF-kappa B). Previously we found that glutathione (GSH) synthesis is induced by cytokines mediated by NF-kappa B (Urata et al. J. Biol. Chem., 1996). Here, we present direct evidence that NF-kappa B activated by ionizing radiation induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate limiting enzyme of GSH synthesis, using T98G human glioblastoma cells. T98G cells have approximately 14-times the level of intracellular GSH of NB9 cells, radiation-sensitive neuroblastoma cells. In T98G cells, 30-Gy of ionizing radiation was required for the activation of NF-kappa B on an electrophoretic mobility shift assay and the induction of gamma-GCS mRNA on Northern blots and a nuclear run-on assay. However, when T98G cells were treated with buthionine sulfoximine, 3-Gy of ionizing radiation stimulated the DNA-binding activity of NF-kappa B and the expression of gamma-GCS. We constructed chimeric genes containing various regions of gamma-GCS promoter gene and the coding region for Luciferase. T98G cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with ionizing radiation. The luciferase activity stimulated by ionizing radiation was found in the gamma-GCS promoter containing the NF-kappa B binding site, whereas not in that containing its mutated site. These results suggest that GSH synthesis is upregulated by ionizing radiation mediated by NF-kappa B and a high concentration of GSH in T98G cells causes downregulation of the NF-kappa B-DNA binding activity in response to ionizing radiation. The irresponsiveness of the intracellular signal transduction cascade to irradiation may be a factor in the resistance of T98G cells to radiation therapy.
...
PMID:Nuclear factor kappa B dependent induction of gamma glutamylcysteine synthetase by ionizing radiation in T98G human glioblastoma cells. 962 82

Previous studies have demonstrated that hypoxia stimulates expression of the c-fos gene in intact animals and isolated cells. The purpose of the present study was to assess the functional significance of c-fos activation during hypoxia. Using antisense c-fos strategy, we tested the hypothesis that c-fos is essential for activation of activator protein-1 transcription factor complex (AP-1) and subsequent stimulation of down stream genes such as tyrosine hydroxylase (TH) gene during hypoxia. Experiments were performed on rat pheochromocytoma 12 (PC12) cells. AP-1 activity was determined by a reporter gene assay using a luciferase expression vector driven by two copies of an AP-1 cis-element (AP-1-Luc). Cells transfected with AP-1-Luc construct were exposed to normoxia (21% O2) or to varying intensities and/or durations of hypoxia. AP-1 activity increased in response to hypoxia. The magnitude of the response depended on the intensity and duration of the hypoxic stimulus. Increases in AP-1 activity could not be elicited in neuroblastoma cells, indicating that hypoxia-induced increase in AP-1 activity is a cell selective phenomenon. Antisense c-fos abolished hypoxia-induced AP-1 activation in PC12 cells. Hypoxia increased tyrosine hydroxylase-chloramphenicol acetyl transferase activity (TH-CAT), and antisense c-fos and mutations at AP-1 binding sites in TH promoter abolished this effect. These results provide direct evidence that c-fos is essential for functional activation of AP-1 and subsequent activation of delayed response genes such as TH in PC12 cells.
...
PMID:Role of c-fos in hypoxia-induced AP-1 cis-element activity and tyrosine hydroxylase gene expression. 972 88

Galanin (GAL) is a 29/30 amino acid residue neuropeptide that regulates a wide variety of neuroendocrine functions. Galanin is expressed in specific populations of neurons in the hypothalamus and other regions of the brain and in numerous peripheral sites. Previous studies in which galanin-reporter genes were transfected into neural crest-derived neuroblastoma and other tumor cells indicated that cell-specific galanin expression is controlled by gene elements on the 5' flanking sequence which enhance and restrict transcriptional activity. To determine how the gene sequences act in vivo, we first determined the distribution of endogenous galanin gene expression in normal mice. Galanin mRNA was detected in several parts of the central nervous system (CNS), and in several peripheral organs, including the pituitary, pancreas, small and large intestine, adrenal gland, lung, tongue, testes, ovary-fallopian tubes, and uterus, but not at detectable levels in the heart, liver, kidney, urinary bladder or skeletal muscle. We then created several lines of transgenic mice which contained either 5 or 0.131 kilobases (kb) of the bovine galanin gene 5' flanking sequence fused to the luciferase (luc) reporter gene (5GAL-luc vs. 0.1GAL-luc mice, respectively) and compared luciferase activity in these and other organs. In some regions of the CNS that expressed high amounts of galanin mRNA, such as the spinal cord, hypothalamus, thalamus, and medulla, transgene expression was significantly higher in 5GAL-luc vs. 0.1GAL-luc mice, whereas in certain other regions of the brain and in all peripheral organs, the ratio was strikingly reversed. It is concluded that 5 kb of flanking sequence contains elements that mediate basal transcriptional activity in certain parts of the CNS, but also contains sequences that restrict expression in many tissues. However, because the larger transgene was expressed at very low levels in some peripheral sites of high galanin expression such as the pituitary, pancreas, adrenal gland, and intestine, it is concluded that sequences on the 5 kb transgene are not sufficient to direct expression to these peripheral tissues in mice.
...
PMID:Tissue-specific enhancement and restriction of galanin gene expression in transgenic mice by 5' flanking sequences. 975 22

Four NPY receptor subtypes have been cloned, and shown to be coupled to both Ca2+ and cAMP. However, very little is known about the downstream elements mediating NPY actions. It has recently been demonstrated in our laboratory that intrahypothalamic (i.h.t.) administration of NPY induces hypothalamic CaM kinase activity, cyclic AMP response element binding protein (CREB) phosphorylation and cyclic AMP response element (CRE) binding activity in rat hypothalamic nuclear proteins. In the present study, we have investigated whether these changes in CRE binding transcriptional factors activated by NPY results in gene regulation using a human neuroblastoma cell line (SK-N-BE2). This cell line which expresses the Y2 subtype of NPY receptors was transfected with a fusion gene containing 1.305 kb of human CRF 5' flanking region with a perfect palindromic CRE site linked to firefly luciferase gene. NPY treatment increased CaM kinase II activity, CREB phosphorylation and CRE binding in these cells. In transfected cells, luciferase activity was also increased by NPY (1.8-4-fold) within 4 h of treatment. Moreover, forskolin (7-30-fold), which stimulates cAMP production, and thapsigargin (6-8-fold), which mobilizes intracellular calcium, also increased luciferase activity within 4 h of treatment. PMA (phorbol-12-myristate-13-acetate), an activator of protein kinase-C, induced luciferase activity by 1.8-fold. NPY augmented forskolin-stimulated luciferase activity from 11- to 15-fold, but had no significant effect on thapsigargin-induced luciferase activity. These findings suggest that activation of protein kinase A (PKA) or CaM kinase leads to the induction of fusion gene. NPY treatment upregulated fusion gene expression through Ca2+ pathway in SK-N-BE2 cell line. Pretreatment with CREB antisense, but not the sense oligodeoxynucleotides, inhibited forskolin-, thapsigargin- and NPY-stimulated luciferase activity. However, CREB sense or antisense oligodeoxynucleotide treatment had no effect on PMA-stimulated luciferase activity. Furthermore, NPY induced CRE binding activity and the expression of CRE containing Y1 receptor gene in SK-N-MC cell line. These findings suggest that NPY can upregulate CRE containing reporter gene including Y1 receptor gene and NPY-induced reporter gene regulation in SK-N-BE2 cells is mediated by intracellular Ca2+ and CREB protein.
...
PMID:NPY upregulates genes containing cyclic AMP response element in human neuroblastoma cell lines bearing Y1 and Y2 receptors: involvement of CREB. 980 24

Receptor for AGE (RAGE) and the polypeptide amphoterin are highly expressed and co-localized in neurons of the developing central nervous system of the rat. In vitro, the interaction of amphoterin with neuronal RAGE induces neurite outgrowth. We tested the hypothesis that interaction of amphoterin with neuronal cells enhances RAGE expression, thereby providing a mechanism by which amphoterin-mediated regulation of RAGE might contribute to promotion of neurite growth and spreading. Incubation of cultured neuroblastoma cells with amphoterin resulted in increased transcription and translation of RAGE, a process largely inhibited in the presence of anti-RAGE IgG but not by nonimmune IgG. To begin to delineate molecular mechanisms underlying these findings, we identified multiple putative binding elements within the 5'-flanking region of the RAGE gene for Sp1, a transcription factor that has been critically linked to the process of normal development. DNase I footprinting and electrophoretic mobility shift assays demonstrated multiple functional Sp1-binding sites within the region -245 to -40 of the RAGE promoter. Transient transfection of cultured SK-N-SH neuroblastoma cells with chimeric 5'-deletion constructs linked to luciferase reporter revealed that the region containing Sp1-binding elements did not contribute uniquely to basal expression of the RAGE gene. Simultaneous mutation of the multiple Sp1-binding elements in this region did not affect basal promoter function; however, promoter responsiveness to amphoterin was markedly attenuated. These results point to Sp1-dependent mechanisms underlying amphoterin-mediated increases in RAGE expression in neuroblastoma cells and further link amphoterin-RAGE interaction to development of the nervous system.
...
PMID:Sp1-binding elements in the promoter of RAGE are essential for amphoterin-mediated gene expression in cultured neuroblastoma cells. 981 79

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>