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 cytotoxic potential of heterologous rabbit antibody directed against mouse serum albumin (MSA) and alpha-fetoprotein (AFP) was investigated in vitro with a cell line (Hepa) derived from the mouse hepatoma BW7756. Anti-AFP in the presence of complement could kill Hepa cells at concentrations of anti-MSA that were virtually nontoxic. The specificity of the anti-AFP was defined by demonstrating that Hepa cell toxicity was dependent upon and paralleled the secretion of AFP in synchronized cultures. Furthermore, neither antiserum could be shown to be significantly toxic to mouse neuroblastoma cells (Neuro-2A). Immunoglobulin purified from pools of antisera was also highly effective in producing cytotoxicity even in a complement-free system. This reaction proceeded more slowly, requiring nearly 48 hr to reach maximum effect in comparison to the 12 hr for complement-mediated toxicity. MSA and AFP are secreted during different phases of the cell cycle. In cultures arrested by isoleucine starvation, labeled AFP appears in the medium 10 hr after release of the blockade in association with S phase. The appearance of labeled MSA is delayed until the first mitosis. Cytotoxic effects of anti-AFP parallel the secretion of AFP in synchronous cultures. Both antisera could be inhibitory to the secretion and synthesis of the proteins of their antigenic specificity. MSA synthesis was more susceptible to this inhibition than was AFP synthesis. The significance of this phenomenon and its association with the differential cytotoxicity of the antiserum are discussed.
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PMID:The influence of antisera specific for alpha-fetoprotein and mouse serum albumin on the viability and protein synthesis of cultured mouse hepatoma cells. 6 16

Neuroblastoma cells were synchronized by a combined isoleucine plus glutamine starvation. Adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was measured under basal conditions and in the presence of dopamine, adenosine and prostaglandin (PG) E1. A clear dissociation occurred between the respective evolution patterns of basal and agonist-stimulated adenylate cyclase activities. The magnitudes of the enzyme response to PGE1, adenosine, and dopamine also exhibited different evolution patterns during the cell cycle. Evolution of adenylate cyclase responsiveness to PGE1 during the cell cycle exhibited striking similarities with the intracellular 3':5'-cyclic AMP changes observed elsewhere. Use of theophylline and fluphenazine as specific inhibitors of adenosine and dopamine, respectively, made it possible to demonstrate that adenosine, dopamine, and PGE1 stimulated adenylate cyclase through independent receptor sites. Furthermore, whatever the stage of the cell cycle, responses to these three agonists were not additive, indicating that the receptors of adenosine, dopamine, and PGE1 control the same adenylate cyclase moieties. The data suggest that adenylate cyclase cell content and enzyme responsiveness to specific agonists can be independently controlled.
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PMID:Adenylate cyclase from synchronized neuroblastoma cells: responsiveness to prostaglandin E1, adenosine, and dopamine during the cell cycle. 26 97

Mouse neuroblastoma cells derived from cholinergic clone NS 20 were synchronized by isoleucine plus glutamine starvation. Basal adenylate cyclase activity increased linearly during the different phases of the cell cycle. Pharmacological data are presented indicating that adenosine, dopamine and prostaglandin E1 control through distinct receptors the same adenylate cyclase activity. The demonstration that basal enzyme activity and its responsiveness to the three agonists tested followed different evolution patterns during the cell cycle suggests that enzyme activity (or content) and activity (or number) of enzyme coupled receptors can be independently modulated.
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PMID:[Adenylate cyclase in synchronized neuroblastoma cells: enzyme response during the cell cycle]. 82 49

Cyclic AMP can profoundly influence the growth and differentiation of neuronal cells in culture. In this study, the relationship between this second messenger signal transduction pathway, cell differentiation, and the expression of a retinoid-responsive, thymosin beta-10 gene was examined. Thymosin beta-10 and cognate mRNA were expressed at high levels in actively proliferating rat B104 neuroblastoma cells cultured in medium containing 10% FCS. These cells were induced to differentiate in the presence of the cAMP analog N6, 2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2-cAMP) (1 mM) and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) (100 microM). Expression of thymosin beta-10 mRNA was markedly inhibited (greater than 90% and 70%, respectively) by these compounds. Addition of sodium butyrate (NaB, 1 mM) indicated that at least part of the inhibitory actions of Bt2-cAMP were due to esterase-induced release of butyrate from this compound. Adenosine (50 microM), a metabolic precursor to endogenous cyclic AMP, also inhibited accumulation of thymosin beta-10 mRNA (to less than 70% of control levels). The inhibitory action of Bt2-cAMP upon thymosin beta-10 mRNA levels was time dependent; levels were inhibited by greater than 50% 24 hours after addition of the cAMP analog and by greater than 90% after 72 hours. Serum starvation (0.2% FCS for seven days) provoked a marked increase in neurite out-growth; this morphological change was also accompanied by a modest inhibition of thymosin beta-10 mRNA accumulation. These findings together with previous observations imply that both cyclic AMP-dependent and retinoid-responsive mechanisms coordinate thymosin beta-10 gene expression during neuroembryogenesis.
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PMID:Influence of cyclic AMP and serum factors upon expression of a retinoid-responsive gene in neuroblastoma cells. 137 94

We have used monoclonal antibodies to statin (S-44) and a cyclin-like protein (S-132) to examine the distribution of these two antigens in proliferating and in nonproliferating populations of cells. We have found that this cyclin-like protein is present in proliferating fibroblasts, whereas statin is absent from these same cell populations; in contrast, in senescent populations of fibroblasts the cyclin-like antigen disappears and statin labeling of nuclei appears. During myogenesis in rat muscle cell cultures, S-132 labeling is present in proliferating myoblasts and disappears after cells fuse and differentiate as multinucleated myotubes. In contrast, statin is absent from proliferating myoblasts, but appears when these cells become postmitotic and begin to differentiate. Similar results were seen during chick myogenesis. We have also found similar results during serum-starvation-induced differentiation in neuroblastoma cells. These results indicate that the cyclin-like protein disappears and statin appears upon commitment to differentiation in vitro, and the presence or the absence of these proteins appears to provide cellular markers for the transition from the proliferative to the nonproliferative state during differentiation.
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PMID:The disappearance of a cyclin-like protein and the appearance of statin is correlated with the onset of differentiation during myogenesis in vitro. 289 89

To study the properties of protein-bound oligosaccharides in neuronally differentiating cells, two model systems were used: murine N1E-115 and N-18 neuroblastoma cells inducible by serum starvation and rat PC12 pheochromocytoma cells inducible by nerve growth factor. Glycopeptides were prepared from cells metabolically labeled with [3H]glucosamine and analyzed by gel filtration. The properties of the high-molecular-weight glycopeptides were studied using enzymatic digestion with neuraminidase and endo-beta-galactosidase. In contrast to other cell lines analyzed, the neuroblastoma and pheochromocytoma lines contained predominantly glycopeptides completely cleavable with endo-beta-galactosidase, which indicated that they were linear-type poly-N-acetyllactosamine glycans. The proportion of these linear chains in the high-molecular-weight fraction increased during neuronal differentiation in both cell systems. The linear nature of the glycans was also correlated with positive anti-i and negative anti-I reactivity of the cells in immunofluorescence microscopy. Specific cell surface labeling for poly-N-acetyllactosamine glycans and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed several glycoprotein components, some of which showed changes during neuronal differentiation. The high proportion of linear poly-N-acetyllactosamine chains in these neuronal cell lines and its increase during neuronal differentiation suggests that these glycans may be a characteristic feature of neuronal or neuronally differentiating cells.
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PMID:Poly-N-acetyllactosamine glycans of cellular glycoproteins: predominance of linear chains in mouse neuroblastoma and rat pheochromocytoma cell lines. 330 6

The mRNA expression of c-myc and N-myc in the human neuroblastoma cell line SH-SY5Y was found not to change appreciably during the cell cycle and was also unaffected by proliferative inhibition induced by serum starvation or polyamine depletion. However, an early (0.5-8.0 h post-induction) transient reduction of c- and N-myc transcripts were observed in these cells upon induction to differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of these neuroblastoma cells with TPA for longer periods (1-8 days), which induces morphological and functional differentiation and growth arrest, was followed by decreased expression of both myc genes. However, the rate of disappearance differed considerably. The N-myc mRNA level was slightly decreased after 4 days and was still detectable 8 days after induction, whereas the c-myc transcript was down-regulated much faster. In contrast, when the cells were exposed to retinoic acid, which results in a maturation along an alternative pathway, the inhibition of N-myc and c-myc expression was similar. The c-fos mRNA expression increased in TPA-treated SH-SY5Y cells and remained high during extended exposure to the drug. The highest c-fos transcript level in induced cells coincided in time with the transient reduction of N-myc and c-myc. Thus, the TPA-induced neuronal differentiation of SH-SY5Y cells was compatible with high c-fos and a substantial N-myc mRNA expression.
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PMID:Different regulation of N- and c-myc expression during phorbol ester-induced maturation of human SH-SY5Y neuroblastoma cells. 332 85

We examined the expression of N-myc, c-myc, and c-src in four embryonic carcinoma (EC) cell lines during different states of cell growth and following induction of in vitro differentiation. N-myc mRNA was detected in undifferentiated cells of four EC cell lines (PCC7, PCC3, PCC4, F9) neither of which showed N-myc gene amplification. No N-myc transcripts could be detected in mRNA prepared from a murine neuroblastoma cell line and from a murine fibroblast line. The level of N-myc mRNA decreased by 85% when PCC7 EC cells were induced by retinoic acid and cAMP treatment to form nerve-like cells. Six days after induction, the PCC7 cells changed into aggregates of neurofilament positive cells with massive neurite outgrowths. At this stage DNA replication had been reduced by more than 95%. The decreased N-myc expression in induced PCC7 cells was parallelled by 300-500% increase in c-src expression. Slowing of cell multiplication by serum starvation, on the other hand, did not affect the level of N-myc or c-src mRNA levels in PCC7 cells. C-myc was expressed in all EC lines except PCC7, which surprisingly did not express c-myc even at an exponential rate of proliferation. Chemical induction of F9 EC cells to form visceral endoderm or parietal endoderm resulted in markedly reduced (85%) levels of N-myc transcripts. A similar decline in c-myc expression was found in differentiated F9 cells. No c-src transcripts were detected in proliferating or differentiated F9 cells. These results suggest that N-myc may be expressed not only in neural development, but also in very early, undetermined embryonic cells. The activation of c-src expression when PCC7 EC cells differentiate into nerve-like cells shows that the pattern of proto-oncogene expression may change during a differentiation process, some proto-oncogenes increasing, others decreasing their representation in the mRNA pool.
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PMID:N-myc and c-src genes are differentially regulated in PCC7 embryonal carcinoma cells undergoing neuronal differentiation. 370 Apr 83

Various tumor cells contain chromatographically distinct isoacceptor tRNA species. To decide whether the tumor-specific species represent an expression of a separate tRNA gene or only an undermodified form of normal tRNAPhe, nucleotide sequences of tRNAPhe isolated from neuroblastoma and normal mouse liver were determined by postlabeling techniques. The results showed identical sequences except for the changes of post-transcriptional modifications in the anticodon loop. Normal mouse liver tRNAPhe contained Cm32, Gm34, and the hypermodified YOH next to the 3' end of the anticodon. On the contrary, tRNAPhe from neuroblastoma contained C32, G34, and, instead of YOH base m1G. A small proportion of tRNAPhe species contained an undermodified YOH base. For the examination of the conditions leading to the undermodified tRNAPhe, Vero cells derived from the kidney of African green monkey in culture were used. In these cells, deprivation of methionine or lysine resulted in changes in tRNAPhe modification similar to those in tumor cells. Ehrlich ascites tumor cells were examined to determine whether the presence of altered tRNAPhe species in various tumors is also the result of starvation of some nutritional factors. Results obtained with these cells showed that tRNAPhe species lacking the Y base disappeared in tumor-bearing mice after intraperitoneal injection with a mixture of amino acids and vitamins. Thus it is concluded that tumor-specific tRNAPhe species are the products of aberrant post-transcriptional modification, not the transcripts of different, normally repressed genes.
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PMID:Alterations in post-transcriptional modification of the Y base in phenylalanine tRNA from tumor cells. 640 57

A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species.
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PMID:Isolation and characterization of a large, neurite-associated glycoconjugate from neuroblastoma cells. 683 76


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