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

After in vitro microtubule assembly of mouse neuroblastoma crude extracts, six protein species migrate in the tubulin region of two-dimensional electrophoregrams. The evolution of these forms after morphological cell differentiation of the clone NIE115 shows two major modifications. Form 5 decreased drastically while form 6 increases during neurite formation. Peptide mapping analysis reveals that forms 5 and 6 are vimentin, a component of intermediate filaments, and beta-tubulin subunit, respectively. Sodium butyrate treatment of NIE115 cells or serum starvation of NIA103 cells, conditions blocking cell division and failing to induce morphological differentiation, prevent any modifications in the relative proportion of these proteins. It is concluded that the changes in the distribution of the tubulin isoforms and vimentin are directly related to neurite formation.
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PMID:Changes in some cytoskeletal proteins during neuroblastoma cell differentiation. 706 11

Murine neuroblastoma cells have been widely used as a model system for neuronal cells as they can be induced to differentiate in culture by various stimuli, such as dibutyryl cyclic AMP (dbcAMP), prostaglandin, and serum starvation. The cells respond with assembly of microtubules, leading to neurite outgrowth, with increased activity of neuronal-specific enzymes, tyrosine hydroxylase, choline acetyltransferase and acetylcholine-esterase, and synthesis of neurotransmitters. The differentiated cells lose tumorigenicity. Cell-to-substratum adhesion is evidently crucial for neurone extension in vitro. Neurite outgrowth is induced by treatments that increase cell-to-substratum adhesion in some neuronal cell cultures. We have now identified the major high molecular weight proteins synthesized and secreted by murine C1300 neuroblastoma cells as fibronectin, laminin and type IV procollagen, of which the latter two were also found to be deposited in pericellular matrix form.
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PMID:Basal lamina glycoproteins are produced by neuroblastoma cells. 743 74

Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been analyzed for their capability to adhere to different extracellular matrix (ECM) components. The GI-CA-N cells adhered to all the tested substrates: laminin (LN), type I and type IV collagen (Coll I, Coll IV), vitronectin (VN), and fibronectin (FN). Conversely LAN-5 cells weakly attached to FN and VN, whilst adhesion on LN and Coll I and IV was strong and induced a rapid elongation of cell processes. By means of RT-PCR and immunoprecipitation we showed that the integrin pattern of these two lines was different and could explain their diversity in adhesion capability. Both cell lines express a large amount of the beta 1 integrin subunit, associated with different alpha chains, probably responsible for their adhesion to some ECM proteins. After treatment of LAN-5 cells with biological differentiating agents, such as gamma-interferon, alone or in combination with tumour necrosis factor-alpha (TNF-alpha), or retinoic acid, the levels of alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 integrin expression were enhanced, while the amount of alpha v remained constant. In contrast, treatment of LAN-5 cells with TNF-alpha, that did not induce any maturation, or starvation in 2% foetal calf serum, that inhibited cell proliferation without affecting neural differentiation, did not induce any change in the integrin assessment. Messenger-RNAs for the two alpha 6 isoforms, A and B, were present in both cell lines. However, in LAN-5 cells, the protein product was neither detectable nor inducible by differentiation. Our results confirm the specific modulation of the alpha 1 beta 1 integrin expression in human neuronal development, and show, for the first time, the involvement of alpha 2 beta 1 and alpha 3 beta 1 heterodimers in this maturational process.
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PMID:Modulation of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrin heterodimers during human neuroblastoma cell differentiation. 769 64

Flow cytometry with the specific monoclonal antibody (MoAb) L31 was used to analyse the expression of HLA class I heavy chains not bound with beta 2-microglobulin (beta 2m) by neuroblastoma (NB) cell lines IMR-32 and LA-N-1. The cells, which express barely detectable amounts of beta 2m-free (L31-positive molecules) and beta 2m-complexed HLA class I antigens (W6.32- and BBM.1-reactive molecules), expressed MHC class I molecules not bound to light chains upon differentiation with either retinoic acid or serum starvation. The expression was not accompanied by an increase of surface heterodimers. Conversely, recombinant interferon-gamma (rIFN-gamma) treatment led IMR-32 and LA-N-1 cells to almost exclusively express beta 2m-complexes HLA class I heavy chains. Surface beta 2m-free MHC class I molecules displayed a molecular mass of approximately 45 kDa and did not bind exogenously added beta 2m. No changes in the synthesis of either HLA class I and beta 2m mRNAs or of L31 proteins were observed in differentiated NB cells, thus suggesting that the surface exposure of unusual HLA class I antigens is regulated post-translationally. These findings indicate that, in addition to activated lymphocytes, the surface expression of beta 2m-free class I heavy chains is a feature of other cell types, such as NB cells.
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PMID:Expression of beta 2m-free HLA class I heavy chains in neuroblastoma cell lines. 831 64

Although neuronal cells are a major target of phorbol ester action, the activity of the various protein kinase C (PKC) isoenzymes have not been studied in detail in human neuroblasts. Differentiation of the LAN-5 human neuroblastoma cell line by interferon-gamma (IFN-gamma) is accompanied by a twofold increase in PKC activity. Since PKC is a multigene family, we investigated which isoforms were expressed in control and differentiated cells, and which of these isoenzymes is involved in neuronal differentiation. We found that: (1) PKC activity is higher in differentiated than in undifferentiated cells; (2) RT-PCR analysis showed the expression of mRNA for PKC alpha, -gamma, -delta, -epsilon and -zeta and the absence of mRNA for beta in untreated LAN-5 cells; (3) Western blot evaluation with PKC isoform-specific antibodies showed the same pattern of PKC expression in non-differentiated cells; (4) Expression of PKC epsilon mRNA was significantly enhanced by IFN-gamma-induced differentiation, while the other isoforms were not affected; (5) Differentiation of LAN-5 cells with IFN-gamma or retinoic acid induced overexpression of the PKC epsilon protein, while inhibition of cell proliferation by fetal calf serum starvation was without effect. These findings suggest that expression of PKC epsilon isoform is tightly coupled with neuronal differentiation and may play a role in the maintenance of the differentiated state.
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PMID:Protein kinase C isoenzymes in human neuroblasts. Involvement of PKC epsilon in cell differentiation. 848 77

Differentiation of NG108-15 neuroblastoma cells following exposure to either 1.5% dimethyl sulfoxide (DMSO)/0.5% fetal bovine serum (FBS) or serum starvation resulted in significant differences in angiotensin (AT) receptor levels and the AT1/AT2 receptor ratio. When NG108 cells were differentiated for 4 days with DMSO/low serum, the number of AT binding sites increased 30-fold compared with the binding levels on undifferentiated (blast) cells. However, cells differentiated by serum starvation for 4 or 14 days resulted in only a modest 2.5- and fivefold increase in AT receptor levels, respectively, over the levels seen with the undifferentiated cells. KD values for all treatment conditions were not significantly different (0.71 +/- 0.11 nM, p = 0.06). Using the AT1 and AT2 isoform-specific receptor antagonists losartan and PD123319, the relative numbers of AT receptor subtypes on undifferentiated and differentiated cells were determined by competitive inhibition against 125I-[Sar1,Ile8]-angiotensin II (sarile). A majority of the AT receptors on undifferentiated NG108 cells were the AT1 subtype (AT1/AT2 receptor ratio of 8:3). Differentiation by serum starvation and DMSO/low serum treatment resulted in fivefold and 30-fold increases in AT receptor levels, respectively, compared with the levels seen with the undifferentiated cells. Although serum starvation increased the total number of AT1 and AT2 receptors, it did not significantly alter the AT1/AT2 receptor ratio. In contrast, differentiation with DMSO/low serum both increased the total number of AT1 and AT2 receptors and reversed the AT1/AT2 receptor ratio (1:3). The increase in AT receptors following differentiation with DMSO/low serum for 4 days was largely accounted for by an 80-fold increase in the AT2 receptor level. Previous studies by Tallant at al. (1991) and Bryson et al. (1992) reported increased AT2 receptor expression following neuroblastoma differentiation with dibutyryl cyclic AMP and DMSO/low serum, respectively, and suggested a role for the AT2 receptor in neuronal differentiation. In the present study, we have extended these earlier observations by demonstrating that the method of differentiation significantly affects both the AT receptor level and the ratio of AT1 to AT2 receptor expression. Finally, our findings indicate that the AT2 receptor is expressed as a consequence of neuronal maturation and dose not mediate morphological differentiation.
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PMID:Differentiation of NG108-15 neuroblastoma cells by serum starvation or dimethyl sulfoxide results in marked differences in angiotensin II receptor subtype expression. 876 61

Aurintricarboxylic acid (ATA) has been reported to protect PC12 cells and cultured neuronal cells from serum starvation-induced cell death, and hippocampal neurons from N-methyl D-aspartate- or ischemia-induced cell death in vivo. We have found that ATA activated tyrosine phosphorylation cascade in PC12 cells as growth factors. Here, we report that ATA prevents cell death under serum starvation and induces tyrosine phosphorylation also in human neuroblastoma SH-SY5Y cells. Furthermore, it was found that erbB4, a member of epidermal growth factor receptor family, is tyrosine-phosphorylated in response to ATA. Both, erbB4 and its ligand, neu differentiation factor (NDF)/ heregulin family, have been reported to be expressed abundantly in nervous system. Thus, tyrosine phosphorylation of erbB4 might explain the neuro-protective activity of ATA.
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PMID:Tyrosine phosphorylation of ErbB4 is stimulated by aurintricarboxylic acid in human neuroblastoma SH-SY5Y cells. 901 63

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.
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PMID:Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates. 925 48

Ras and Rho family GTPases have been ascribed important roles in signalling pathways determining cellular morphology and growth. Here we investigated the roles of the GTPases Ras, Cdc42, Rac1, and Rho and that of phosphatidylinositol 3-kinase (PI 3-kinase) in the pathway leading from serum starvation to neurite outgrowth in N1E-115 neuroblastoma cells. Serum-starved cells grown on a laminin matrix exhibited integrin-dependent neurite outgrowth. Expression of dominant negative mutants of Ras, PI 3-kinase, Cdc42, or Rac1 all blocked this neurite outgrowth, while constitutively activated mutants of Ras, PI 3-kinase, or Cdc42 were each sufficient to promote outgrowth even in the presence of serum. A Ras(H40C;G12V) double mutant which binds preferentially to PI 3-kinase also promoted neurite formation. Activated Ras(G12V)-induced outgrowth required PI 3-kinase activity, but activated PI 3-kinase-induced outgrowth did not require Ras activity. Although activated Rac1 by itself did not induce neurites, neurite outgrowth induced by activated Cdc42(G12V) was Rac1 dependent. Cdc42(G12V)-induced neurites appeared to lose their normal polarization, almost doubling the average number of neurites produced by a single cell. Outgrowth induced by activated Ras or PI 3-kinase required both Cdc42 and Rac1 activity, but Cdc42(G12V)-induced outgrowth did not need Ras or PI 3-kinase activity. Active Rho(G14V) reduced outgrowth promoted by Ras(G12V). Finally, expression of dominant negative Jun N-terminal kinase or extracellular signal-regulated kinase did not inhibit outgrowth, suggesting these pathways are not essential for this process. Our results suggest a hierarchy of signalling where Ras signals through PI 3-kinase to Cdc42 and Rac1 activation (and Rho inactivation), culminating in neurite outgrowth. Thus, in the absence of serum factors, Ras may initiate cell cycle arrest and terminal differentiation in N1E-115 neuroblastoma cells.
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PMID:Phosphatidylinositol 3-kinase, Cdc42, and Rac1 act downstream of Ras in integrin-dependent neurite outgrowth in N1E-115 neuroblastoma cells. 1059 18

The sensitive-to-apoptosis gene (SAG) was initially identified as a redox-inducible, apoptosis-protective protein and subsequently found to be the second family member of regulator of cullins (ROC)/RING box protein (Rbx)/Hrt, which acts as a component of E3 ubiquitin ligase. We report here that SAG promoted cell growth under serum starvation. Microinjection of SAG mRNA into quiescent NIH/3T3 cells induced S-phase entry as determined by [(3)H]-thymidine incorporation. Likewise, overexpression of SAG by either adenovirus infection of immortalized human epidermal keratinocytes (Rhek-1) or DNA transfection of SY5Y human neuroblastoma cells induced cell proliferation under serum starvation. Because cyclin-dependent kinase inhibitors (CKIs), including p21, p27, and p57, are degraded through the ubiquitin pathway, we tested whether SAG-induced cell growth is associated with CKI degradation. Although there was no significant difference in the levels of p21 and p57 between the vector controls and SAG-overexpressing cells, serum starvation induced 10- to 18-fold accumulation of p27 in control Rhek-1 cells. Accumulation of p27 was remarkably inhibited (only 2 to 5-fold) in SAG-infected cells. Inhibition of p27 accumulation was also observed in stably SAG-overexpressing SY5Y cells. Significantly, SAG-associated inhibition of p27 accumulation was largely abolished by the treatment with a proteasome inhibitor. In vivo binding of SAG and Skp2, an F-box protein that promotes p27 ubiquitination, was detected, and the binding was enhanced in SAG-overexpressing cells grown under serum starvation. Thus, SAG-induced growth with serum withdrawal appears to be associated with SAG-mediated p27 degradation. Mol. Carcinog. 30:37-46, 2001.
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PMID:Promotion of S-phase entry and cell growth under serum starvation by SAG/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: association with inhibition of p27 accumulation. 1125 62


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