Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of specific AII receptors in 6 different human neuroblastoma cell lines was investigated using binding, cAMP and [Ca2+]i studies. We found high affinity (0.1 nM), low capacity ((1-2).10(3) sites/cell) binding sites for [125I](Sar-1,Ile-8)AII in one half of the cell lines studied. In the positive cell lines mathematical modeling of multiple competition curves among AII and analogs strongly indicated the presence of a homogenous class of sites, i.e., AT1 receptors. The presence of AT1 receptors was further substantiated by AII-induced inhibition of VIP-stimulated cAMP levels and by AII-evoked [Ca2+]i transient. The density of AT1 receptors in neuroblastoma cells was not affected by treatment with pertussis toxin and retinoic acid but was significantly increased by subacute treatment with VIP. In neuroblastoma cells, AII does not stimulate DNA synthesis, suggesting other roles rather than mitogenesis. Neuroblastoma cells represents an interesting model to investigate the function of AII in neural crest derived tissues.
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PMID:Identification and characterization of functional angiotensin II receptors in human neuroblastoma cells. 765 93

The neuropoietic cytokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) regulate VIP gene expression through a cytokine response element (CyRE) which interacts with members of the STAT transcription factor family. The CyRE STAT site is, however, insufficient to mediate full transcriptional activation by CNTF/LIF, suggesting that other sequences and nuclear proteins are also important. As C/EBP proteins participate in the transcriptional effects of the related cytokine, interleukin-6, we investigated the role of possible C/EBP-binding sites in the response of the VIP CyRE to CNTF/LIF. Using DNase I footprinting, transactivation studies, DNA mobility shift assays, and mutational analysis, three sites within the VIP CyRE were identified as C/EBP-related binding sites and shown to be important to CNTF/LIF-mediated transcriptional activation. The CyRE C/EBP-related sites interact with nuclear proteins from the human neuroblastoma cell line, NBFL, including a novel, protein synthesis-dependent, nuclear protein complex, induced by CNTF treatment. These nuclear proteins are not, however, recognized by antisera to known C/EBP proteins. Therefore, other nuclear proteins regulated by independent pathways act in concert with the JAK-STAT pathway to mediate CNTF/LIF regulation of VIP gene expression through the CyRE.
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PMID:C/EBP-related sites in addition to a STAT site are necessary for ciliary neurotrophic factor-leukemia inhibitory factor-dependent transcriptional activation by the vasoactive intestinal peptide cytokine response element. 771 8

VIP is a widely distributed neuropeptide of 28 amino acids, whose central part is proposed to be an amphiphilic alpha-helix. In order to gain an understanding of the effect of this alpha helix on receptor binding and stimulation, a human VIP analog has been designed in which the residues 12 to 19 were replaced by a spacer of the same length, (gamma-aminobutyryl)2. This peptide altered neither the basal guinea pig tracheal smooth muscle tonus nor the VIP-induced relaxation. Conversely, the VIP analog was found to displace VIP from its binding sites on LA-N-2 human neuroblastoma cells (VIP IC50: 5.4 nM; VIP analog IC50: 52.2 nM) and to inhibit the VIP-induced cyclic AMP production of 58 +/- 15% at 1 microM and 95 +/- 2% at 10 microM. It seems that the alpha helix structure might only play the role of a spacer holding the important residues, at the N- and C-ends, respectively, at an appropriate distance. In the VIP analog structure, the (gamma-aminobutyryl)2 chain introduced in place of the alpha helix plays the role of adequate spacer to bind the LA-N-2 receptors but probably does not induce the active conformation for receptor stimulation. The lack of VIP analog effects on the tracheal receptors related to relaxation argues for a possible heterogeneity of VIP receptors on a pharmacological basis.
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PMID:A new vasoactive intestinal peptide antagonist discriminates VIP receptors on guinea pig trachea and human neuroblastoma cells. 797 35

To investigate the presence of biologically active somatostatin (SS) receptors in neural crest-derived tumors, radioligand binding studies, cyclic AMP accumulation, intracellular calcium, and growth assays were performed in eight human neuroblastoma (NB) cell lines. Mathematical modeling of binding experiments strongly indicates the presence of heterogeneity of sites. The first site (SSR1) is present in 40% of the NB cell lines and binds with low capacity (0.5 pmol/mg protein) and high affinity (0.1-1 nM) SS14, SS28, and analogues. The second site (SSR2) is a high capacity site (200 pmol/mg protein), widely distributed in all of the cell lines investigated, that shows relative selectivity yet low affinity (100 nM) for SS14, SS28, and [D-Trp8]SS14 without any apparent biological activity. SSR1 is coupled to a pertussis toxin-sensitive G protein, inhibits forskolin- or VIP-stimulated adenylate cyclase activity, decreases intracellular free calcium, and mediates inhibition (30%) of both DNA synthesis and cell growth. Analysis of cell cycle distribution in aphidicolin-synchronized SSR1-positive NB cells indicated that this inhibitory effect is partially mediated by a transient accumulation in G0-G1. Our data indicate high affinity binding sites for SS14, and analogues are present and biologically active in a subset of NB cells.
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PMID:Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines. 826 33

Pituitary adenylate cyclase activating polypeptide (PACAP) is a newly discovered neuropeptide which exists in two biologically active forms: PACAP-38 consisting of 38 amino acids and PACAP-27, a peptide corresponding to the N-terminal 27 amino acids of PACAP-38. Both PACAPs are derived from a 176 amino acid precursor (preproPACAP) which in addition gives rise to a 29 amino acid peptide, designated PACAP-related peptide (PRP). The presence of the three preproPACAP-derived peptides (PACAP-38, PACAP-27 and PRP) in tumour tissue from nine patients with VIP-producing tumours (pancreatic carcinoma, neuroblastoma, ganglioneuroma and pheochromocytoma) and eleven patients with non-VIP-secreting tumours (gastrinoma, glucagonoma, somatostatinoma, neuroblastoma) was examined by specific radioimmunoassays. In seven out of the nine VIP-secreting tumours elevated concentrations of all the three preproPACAP-derived peptides were found compared with normal tissue, while the concentrations in the non-VIP-secreting tumours were within the normal range. PACAP-38 was in all cases the dominating peptide, the concentration ranging from 41 to 3606 pmol/g. When tumour extracts were fractionated on Sephadex G50 column, tricine gel electrophoresis or reverse-phase HPLC immunoreactive components corresponding to synthetic PACAP-38, PACAP-27 and human PRP were identified, suggesting that preproPACAP was fully processed. Immunocytochemical examination showed PACAP-immunoreactive cells in the tumour tissue which also stained for VIP. This co-localization of PACAP and VIP was confirmed by double-staining experiments on the same sections, demonstrating PHM/VIP mRNA and PACAP-immunostaining in the same cells.
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PMID:PreproPACAP-derived peptides occur in VIP-producing tumours and co-exist with VIP. 857 31

Clonal human neuroblastoma cells SH-IN undergo a very conspicuous phenotypic change in culture. Large substrate-adherent cells with a slow growth rate give rise to small cells emerging in focal aggregates and growing to high cell densities. This is accompanied by a dramatic switch in the expression of receptors for the structurally related neuropeptides VIP (vasoactive intestinal polypeptide) and PACAP (pituitary adenylate cyclase activating polypeptide). Large cells expressed mainly PACAP-specific receptors that triggered stimulation of intracellular cGMP production. On the other hand, polyvalent VIP/PACAP receptors positively coupled to adenylate cyclase were mostly observed in the small cells. Both neuropeptides stimulated cell proliferation in large and small cells. These data, together with the previous demonstration of autocrine/paracrine actions of VIP and PACAP in human neuroblastomas, support the idea that these neuropeptides may participate in the establishment of the apparent phenotype in these cancer cells.
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PMID:Switches in the expression and function of PACAP and VIP receptors during phenotypic interconversion in human neuroblastoma cells. 891 56

Peripheral neuroepitheliomas are rare malignant tumors of presumed neural crest origin, arising outside the central and sympathetic nervous system. We present herein a case of a young man with diffuse peripheral neuroepithelioma of the abdominal cavity. Although we twice attempted a debulking procedure on this patient, and treated him with alternating VIP-CAV combined chemotherapy, his disease showed a relentless course without responding to any treatment. The development of peripheral neuroepithelioma in the abdominal cavity is an extremely rare occurrence. These rare malignant tumors, of presumed neural crest origin, arise outside the central and sympathetic nervous systems (1). Other names for this tumor are: extracranial primitive neuroectodermal tumor (PNET), Askin tumor, peripheral or adult neuroblastoma (2,3,4). We present a case of a young man with diffuse development of this tumor in the abdominal cavity.
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PMID:Peripheral neuroepithelioma developing in the abdominal cavity. 892 Jul 88

The ability of cAMP-dependent protein kinase (PKA) to phosphorylate type I, II, and III inositol 1,4,5-trisphosphate (InsP3) receptors was examined. The receptors either were immunopurified from cell lines and then phosphorylated with purified PKA or were phosphorylated in intact cells after activating intracellular cAMP formation. The former studies showed that the type I receptor was a good substrate for PKA (0.65 mol Pi incorporated/mol receptor), whereas type II and III receptors were phosphorylated relatively weakly. The latter studies showed that despite these differences, each of the receptors was phosphorylated in intact cells in response to forskolin or activation of neurohormone receptors. Detailed examination of SH-SY5Y neuroblastoma cells, which express >/=99% type I receptor, revealed that minor increases in cAMP concentration were sufficient to cause maximal phosphorylation. Thus, VIP and pituitary adenylyl cyclase activating peptide (acting through Gs-coupled pituitary adenylyl cyclase activating peptide-I receptors) were potent stimuli of type I receptor phosphorylation, and remarkably, even slight increases in cAMP concentration induced by carbachol (acting through Gq-coupled muscarinic receptors) or other Ca2+ mobilizing agents were sufficient to cause phosphorylation. Finally, PKA enhanced InsP3-induced Ca2+ mobilization in a range of permeabilized cell types, irrespective of whether the type I, II, or III receptor was predominant. In summary, these data show that all InsP3 receptors are phosphorylated by PKA, albeit with marked differences in stoichiometry. The ability of both Gs- and Gq-coupled cell surface receptors to effect InsP3 receptor phosphorylation by PKA suggests that this process is widespread in mammalian cells and provides multiple routes by which the cAMP signaling pathway can influence Ca2+ mobilization.
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PMID:Phosphorylation of inositol 1,4,5-trisphosphate receptors by cAMP-dependent protein kinase. Type I, II, and III receptors are differentially susceptible to phosphorylation and are phosphorylated in intact cells. 948 97

The vasoactive intestinal peptide cytokine response element (VIP CyRE) is responsible for mediating the transcriptional induction of the VIP gene to the neuropoietic cytokines leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF). In investigating the sequence and function of the CyRE, we found a region of DNA with homology to the distal NFAT site in the IL-2 promoter. In this paper we characterize this sequence and show that the VIP NFAT site recognizes T cell NFAT with similar affinity to the previously characterized IL-2 NFAT site. However, despite its location in the middle of the CyRE, we find no CNTF/LIF induced binding to it. Instead we show that in NBFL neuroblastoma cells, the calcium ionophore A23187 induces a protein to bind to the VIP NFAT site. This A23187-mediated induction of nuclear protein binding to an NFAT oligonucleotide is dependent on extracellular calcium but not dependent on de novo protein synthesis. Thus, this protein has the characteristics of an NFAT-like protein and is recognized by an NFAT3-specific antiserum suggesting that it is indeed an NFAT protein. The location of the NFAT site in the VIP CyRE suggests that this may be one mechanism through which different signaling pathways engage in cross talk to alter VIP gene transcription.
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PMID:NFAT interactions with the vasoactive intestinal peptide cytokine response element. 955 32

The cis-acting elements of the VIP gene important for basal and stimulated transcription have been studied by transfection of VIP-reporter gene constructs into distinct human neuroblastoma cell lines in which VIP transcription is constitutively high, or can be induced to high levels by protein kinase stimulation. The 5.2 kb flanking sequence of the VIP gene conferring correct basal and inducible VIP gene expression onto a reporter gene in these cell lines was systematically deleted to define its minimal components. A 425-bp fragment (-4656 to -4231) fused to the proximal 1.55 kb of the VIP promoter-enhancer was absolutely required for cell-specific basal and inducible transcription. Four additional components of the VIP gene were required for full cell-specific expression driven by the 425 bp TSE (region A). Sequences from -1.55 to -1.37 (region B), -1.37 to -1.28 (region C), -1.28 to -.094 (region D), and the CRE-containing proximal 94 bp (region E) were deleted in various combinations to demonstrate the specific contributions of each region to correct basal and inducible VIP gene expression. Deletion of region B, or mutational inactivation of the CRE in region E, resulted in constructs with low transcriptional activity in VIP-expressing cell lines. Deletion of regions B and C together resulted in a gain of transcriptional activity, but without cell specificity. All five domains of the VIP gene were also required for cell-specific induction of VIP gene expression with phorbol ester. Gelshift analysis of putative regulatory sequences in regions A-D suggests that both ubiquitous and neuron-specific trans-acting proteins participate in VIP gene regulation.
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PMID:Cis-regulatory elements controlling basal and inducible VIP gene transcription. 992 92


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