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 c-Myc protein is a potential activator of transcription, with the ability to bind in a heterodimer form with Max to DNA sequences containing the core hexanucleotide sequence CAC(G/A)TG. These properties are shared with L-Myc, a homologous oncoprotein expressed in small cell lung carcinoma cells; with N-Myc, expressed in neuroblastoma cells; and with avian v-Myc, the c-Myc homolog expressed by a chicken retrovirus. The c-Myc, and probably v-Myc, proteins also have nonspecific DNA binding function, which may improve the kinetics of specific DNA binding. Curiously, this domain appears not to be conserved in L-Myc or N-Myc [22]. The data that have accumulated to date are consistent with a model in which a c-Myc/Max heterodimer positively regulates the transcription of growth-related genes, with Max homodimer functioning as a negative regulator of the same genes (Fig. 4) [55]. Max is expressed constitutively at low levels, whereas c-Myc is expressed at low levels in quiescent cells, but high levels of c-Myc are induced by mitogenic stimulation [56]. Thus, in proliferating cells c-Myc/Max heterodimers might bind to the regulatory elements of growth-related genes, where the c-Myc TAD might stimulate transcription. Conversely, in quiescent cells with little c-Myc present, Max homodimers might predominate. They might bind to exactly the same regulatory elements, but due to the apparent absence of a TAD in Max [36], transcription might be repressed. Validation of this model will require the demonstration of clear regulation of a physiological promoter of a growth-related gene by c-Myc/Max. Although it is widely believed that Myc proteins function as transcriptional activators, this hypothesis has only been conclusively supported recently [57, 58]. A theory that c-Myc plays a role in DNA replication is not as well substantiated at this point. It is even possible that Myc might be involved in both transcription and replication. Although the function of these fascinating proteins has been enigmatic for a decade, the rate of progress in our understanding of Myc function is accelerating. Such progress will undoubtedly lead to a deeper appreciation of this protein, which lies at the crossroads of cellular proliferation and oncogenesis.
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PMID:DNA binding by the Myc oncoproteins. 136 64

The N-myc gene is amplified in several types of human tumors. To assess the role of the N-myc gene in the transformation of normal human cells, we transfected an N-myc expression vector into diploid human fibroblasts. Transfected clones were isolated and found to express the N-myc gene at levels similar to those seen in a tumor cell line (neuroblastoma LA-N-1) which contains an amplified N-myc gene. The level of N-myc expression decreased as the N-myc clones senesced. Clones expressing N-myc had an increased saturation density and an altered morphology but did not have an extended lifespan. Under low serum conditions, neither the clones expressing N-myc nor the control cells showed anchorage-dependent growth. Clones expressing N-myc were compared to control cells to determine if different growth factors would affect the ability of cells to grow in soft agarose. Clones expressing N-myc and the control cells did not grow in soft agarose supplemented with epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). However, compared to control cells, clones expressing N-myc grew in agarose 2.8- to 18-fold higher in response to basic fibroblast growth factor (bFGF) and 5.5- to 55-fold higher in response to platelet-derived growth factor B-chain homodimer (PDGF-BB).
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PMID:N-myc oncogene enhances mitogenic responsiveness of diploid human fibroblasts to growth factors but fails to immortalize. 186 69

This study was made to compare the physical and chemical properties of amalgam with those of gallium alloy in which the invented liquid alloy containing the three fundamental components of Ga-Sn-In or Ga-Sn-In-Ag were used instead of mercury. Experiment 1. The physical and chemical properties were investigated after the liquid gallium alloy and high copper amalgam powder were mixed. The following results were obtained; 1) The invented gallium alloy group showed expansion in dimensional changes immediately after mixing. This alloy group showed the same compressive and diametral tensile strength as those in amalgam after 7 days. 2) This alloy group showed slightly more corrosion weight loss in 0.05% HCl and 1% lactic acid solutions than that in amalgam, but this alloy group showed the same corrosion weight loss in 1% NaCl solution and artificial saliva as in amalgam. Also this alloy group showed more discoloration (delta E, NBS) in 0.1% Na2S solution than that in amalgam, but this showed the same degree of discoloration in artificial saliva. Experiment 2. The physical and chemical properties were investigated after the same liquid gallium alloy and Ag-Pd-Sn-Cu-Zn alloy powder were mixed. The following results were obtained; 1) The invented gallium alloy group showed expansion in dimensional changes immediately after mixing. This showed superior quality in compressive and diametral tensile strength as compared with those of amalgam. 2) The invented gallium alloy showed slightly more corrosion weight loss in 0.05% HCl and 1% lactic acid solutions than that in amalgam, but this alloy group showed the same corrosion weight loss in 1% NaCl solution and artificial saliva as in amalgam. Also this alloy group showed more discoloration (delta E, NBS) in 0.1% solution than that in amalgam, but it was the same in artificial saliva.
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PMID:[A basic study on gallium alloys for dental restorations. Improvement of liquid gallium alloy]. 248 4

We investigated whether polymorphonuclear leukocytes (PMN) are able to kill human neuroblastoma cells either directly or if coated with antibody MAb 14.18 that recognizes ganglioside GD2 present on the cell surface of most neuroblastoma cells. Neuroblastoma cells could not be destroyed directly, whereas in the antibody-dependent reaction (ADCC-reaction) they were easily eliminated. In order to answer the question whether reactive oxygen intermediates are involved in this process, chemiluminescence measurements were performed. Compared to the signals that could be measured using opsonized zymosan as stimulus, only weak CL-signals could be registered during the ADCC reaction. Pretreatment of PMN with granulocyte-macrophage colony stimulating factor (GM-CSF) enhanced the CL-signals, catalase and SOD reduced it; however, cell killing was only slightly influenced in the presence of catalase and superoxide dismutase. These data suggested that reactive oxygen compounds do not play a prominent role in the killing process. Definitive evidence for this suggestion could be obtained using PMN from a patient with chronic granulomatous disease (CGD): MAb 14.18 coated neuroblastoma cells could be killed effectively, but no CL-signal could be registered, either in the ADCC-reaction or using opsonized zymosan as stimulus.
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PMID:Effects of granulocytes on human neuroblastoma cells measured by chemiluminescence and chromium-51 release assay. 272 18

Activating transcription factor-3 (ATF-3) is one member of a large family of leucine zipper transcription factors which bind to promoters responsive to cAMP and phorbol ester at the related cAMP (CRE) and phorbol ester response elements. We report here that ATF-3 is coexpressed with the neuropeptide precursor proenkephalin in human neuroblastoma SK-N-MC cells. Cotransfection experiments indicate that activation of proenkephalin gene expression by ATF-3 is dependent upon both the catalytic subunit of the cAMP-dependent protein kinase and the CRE-2 element. The CRE-2 element is essential for second messenger-inducible expression and is known to bind AP-1-like transcription factors. ATF-3 expressed in bacteria or from rabbit reticulocyte lysates binds to the proenkephalin CRE-2 element as a homodimer and as a heterodimer with Jun-D, another activator of proenkephalin transcription. ATF-3 stimulates binding of Jun-D to the proenkephalin CRE-2 element and acts synergistically with Jun-D to induce proenkephalin gene expression. Sequential immunoprecipitations of ATF-3 from SK-N-MC cells expressing proenkephalin indicate that ATF-3 is complexed with Jun-D in vivo and that both proteins are highly phosphorylated. Together, our results suggest that ATF-3 may play an important role in the regulation of gene expression by cAMP-dependent intracellular signaling pathways.
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PMID:Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression. 815 31

Human or mouse epidermal keratinocytes NHEK or Pam212 was less susceptible to ultraviolet (UV)-B irradiation than mouse neuroblastoma NAs1 cells in culture, undergoing apoptosis-like cell death as shown by cell fragmentation and cell membrane integrity disruption. UV susceptibility was appreciably reduced by the reactive oxygen species (ROS)-scavenger L-ascorbic acid-2-phosphate (Asc2P) endowed with long-lasting functions but not by L-ascorbic acid (Asc) for each cell type. DehydroAsc reduced UV susceptibility of Pam212 or NAs1 established cell lines but not of normal diploid NHEK cells destined to be thereafter submitted to cellular senescence. The susceptibility reduction may not be ascribed to extracellular Asc2P or DehAsc, which was removed by aspirating and/or rinsing upon irradiation after the intracellular channelyzer analysis and dead cell-specific DNA-intercalator ethidium homodimer/fluorometry, respectively. Thus, the three cell types differed in UV susceptibility partly because of their different ROS-scavenging abilities, which may be potently promoted by Asc2P or dehydroAsc but not Asc.
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PMID:Differential susceptibility of epidermal keratinocytes and neuroblastoma cells to cytotoxicity of ultraviolet-B light irradiation prevented by the oxygen radical-scavenger ascorbate-2-phosphate but not by ascorbate. 877 35

Nitric oxide (NO) challenge to human neuroblastoma cells (SH-SY5Y) ultimately results in apoptosis. Tumor suppressor protein p53 and cell cycle inhibitor p21 accumulate as an early sign of S-nitrosoglutathione-mediated toxicity. Cytochrome c release from mitochondria and caspase 3 activation also occurred. Cells transfected with either wild type (WT) or mutant (G93A) Cu, Zn-superoxide dismutase (Cu,Zn-SOD) produced comparable amounts of nitrite/nitrate but showed different degree of apoptosis. G93A cells were the most affected and WT cells the most protected; however, Cu, Zn-SOD content of these two cell lines was 2-fold the SH-SY5Y cells under both resting and treated conditions. We linked decreased susceptibility of the WT cells to higher and more stable Bcl-2 and decreased reactive oxygen species. Conversely, we linked G93A susceptibility to increased reactive oxygen species production since simultaneous administration of S-nitrosoglutathione and copper chelators protects from apoptosis. Furthermore, G93A cells showed a significant decrease of Bcl-2 expression and, as target of NO-derived radicals, showed lower cytochrome c oxidase activity. These results demonstrate that resistance to NO-mediated apoptosis is strictly related to the level and integrity of Cu,Zn-SOD and that the balance between reactive nitrogen and reactive oxygen species regulates neuroblastoma apoptosis.
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PMID:Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells. 1067 49

The aim of this study was to clarify retinoid receptor mechanisms mediating the effects of 9-cis retinoic acid (RA) and investigate the ability of RAR- and RXR-specific analogues to induce differentiation and inhibit proliferation in neuroblastoma cells. Differentiation and the inhibition of proliferation by 9-cis RA, but not all-trans RA, were inhibited by the RXR-homodimer antagonist LG745. The RXR-specific agonist LGD1069 was ineffective at inducing differentiation or inhibiting proliferation, but showed marked synergism with RAR-specific agonists with respect to inhibiting proliferation. These data suggest that the effects of 9-cis RA are mediated via both RXR-homodimers and heterodimers. However, combinations of RAR- and RXR-selective analogues were not as effective at promoting differentiation. This study indicates that different receptor mechanisms are involved in retinoid-induced differentiation and inhibition of proliferation in neuroblastoma cells.
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PMID:Receptor mechanisms mediating differentiation and proliferation effects of retinoids on neuroblastoma cells. 1067 34

MPP(+), an active metabolite of MPTP, causes a dopaminergic neuronal degeneration similar to that observed in Parkinson's disease. Current data suggest that MPP(+)-induced cytotoxicity may be mediated by oxygen free radicals. To evaluate this hypothesis, we first investigated whether MPP(+) could cause oxidative stress by producing oxygen free radicals in the SH-SY5Y, human neuroblastoma cell line. MPP(+) was toxic to the cells dose-dependently but did not increase the level of lipid peroxidation at toxic concentrations. Second, we examined the effects of various antioxidants and an inhibitor of nitric oxide synthase (NOS) on the development of MPP(+) cytotoxicity. Pretreatment with antioxidants such as ascorbic acid, Trolox, phenyl-tertiary-butyl-nitrone (PBN), which show protective effects on tert-butyl hydroperoxide (tBOOH) toxicity did not attenuate MPP(+) cytotoxicity. Similarly, the combination of antioxidant enzymes, SOD and catalase (50 U/ml, respectively), did not protect the cells from the toxic action of MPP(+). Also N-nitro-l-arginine methyl ester (NAME), a competitive inhibitor of NOS, and combined incubation with NAME and antioxidant enzymes failed to attenuate MPP(+) cytotoxicity. On the other hand, a sublethal dose of MPP(+) potentiated iron and H(2)O(2)-induced cytotoxicity. These results suggest that oxygen free radicals may not be a primary cause of MPP(+)-induced cell death but that MPP(+) increases the vulnerability of cells to oxidative stress.
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PMID:MPP(+) increases the vulnerability to oxidative stress rather than directly mediating oxidative damage in human neuroblastoma cells. 1096 95

HAND2 (dHAND) is a basic helix-loop-helix (bHLH) transcription factor expressed in numerous tissues during development including the heart, limbs, and a subset of neural crest derivatives. Functional analysis has shown that HAND2 is involved in development of the branchial arches, heart, limb, vasculature, and nervous system. Although it is essential for development of numerous tissues, little is known about its mode of action. To this end, we have characterized HAND2 transcriptional regulatory mechanisms. Using mammalian one-hybrid analysis we show that HAND2 contains a strong transcriptional activation domain in the amino-terminal third of the protein. Like most tissue-restricted bHLH factors, HAND2 heterodimerizes with the broadly expressed bHLH factors, the E-proteins. We determined the consensus DNA binding site of HAND2 and show that HAND2 binds a subset of E-boxes as a heterodimer with E12. Yeast two-hybrid screening of a neuroblastoma cDNA library for HAND2-interacting proteins selected HAND2 and numerous additional members of the E-protein family. Although HAND2 homodimer formation was confirmed by in vitro analysis, HAND2 fails to homodimerize in a mammalian two-hybrid assay but demonstrates robust HAND2/E12 interaction. We conclude that HAND2 functions as a transcription activator by binding a subset of E-boxes as a heterodimer with E-proteins.
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PMID:The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer. 1181 99


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