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)

Adriamycin, an anticancer agent acting on topoisomerase II, promotes the arrest of cell division and neurite extension in a "neurite-minus" murine neuroblastoma cell line, N1A-103. This morphological differentiation is accompanied by a blockade in the S phase of the cell cycle, modification of the amount of peripherin, and appearance of the beta 7-tubulin isoform. Yet, adriamycin-induced N1A-103 cells fail to express other neuronal markers, such as long-lasting Ca2+ channels, synaptophysin, and the shift in the proportion of the beta'1 tubulin isoform to the beta'2 isoform, whose appearance parallels the terminal differentiation of the wild type neuroblastoma cell line N1E-115. Hence, a comparison of the behavior of these two cell lines leads to the proposal that there are two programs of neuroblastoma differentiation: one where expression is triggered by the arrest of cell division and which is observed in adriamycin-induced N1A-103 variant cells, and the other, presumably occurring further downstream, which would involve further changes in morphogenesis and acquisition of new electrophysiological properties.
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PMID:Adriamycin promotes neurite outgrowth in the "neurite-minus" N1A-103 mouse neuroblastoma cell line. 133 Jun 60

The nonobese diabetic (NOD) mouse, in which major histocompatibility complex genes may be involved in the susceptibility to diabetes, has been developed as a model of autoimmune diabetes. The NOD mouse expresses I-A-encoded class II major histocompatibility complex antigens, which differ from those of other mouse haplotypes by the presence of a serine at position 57 of the A beta chain. Identifying islet autoantigens may help elucidate the role of class II antigens in the activation of autoreactive T cells and, thus, in the development of diabetes. We have detected autoantibodies directed against a 58-kDa islet cell antigen in NOD mice but not in other strains, including lupus-prone mice. Apart from insulin-secreting cells, the 58-kDa antigen was only found to be expressed by neuroblastoma cells and was identified as peripherin, an intermediate filament protein previously characterized in well-defined neuronal populations. This autoantigen cross-reacted with I-Anod class II antigens, suggesting that it may contribute to defective self-tolerance of islet beta cells in the NOD mouse.
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PMID:Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products. 172 86

Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative.
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PMID:Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line. 193 96

Peripherin, an intermediate filament protein, described recently, is expressed in well defined neuronal populations. We studied the phosphorylation, in vivo, of this protein in mouse neuroblastoma NIE 115 cell line and in sympathetic neurons labelled with [32P]-orthophosphate. The autoradiograms of proteins separated on two-dimensional polyacrylamide gels were compared with the Coomassie-blue stainings. The results show that peripherin occurs as a mixture of phosphorylated and non-phosphorylated isoforms, and that these forms coexist in both differentiated and non-differentiated cells. We demonstrate by cleavage at the unique tryptophan residue, a characteristic shared by most other intermediate filament proteins (IFP), that the phosphorylation sites are located on the amino-terminal half of peripherin as it is for vimentin and desmin. These results are discussed in relation to the organization of the filamentous network constituted by peripherin.
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PMID:Phosphorylation of peripherin, an intermediate filament protein, in mouse neuroblastoma NIE 115 cell line and in sympathetic neurons. 271 95

Three cDNA clones of 1.6 (3u), 1.2 (5g) and 0.6 (5b) kbp, specific for peripherin, a neuronal intermediate filament protein (IFP), have been isolated from a murine neuroblastoma cell lambda gt11 library by immunoscreening using peripherin antiserum. Antibodies eluted from the fusion proteins produced by clones 3u and 5g recognize the peripherin spots on immunoblots. Where they overlap the three cDNAs have identical sequences. cDNA 5g exhibits the closest homology to type III IFP cDNAs. cDNA 3u is identical to the corresponding region of cDNA 5g, except for the insertion of a 96 bp fragment at a position corresponding to the junction of exons 4 and 5 in type III IFP cDNAs. cDNA 5b is also identical to the corresponding region of cDNA 5g, except for the deletion of a 62 bp fragment at the junction of exons 8 and 9 in type III IFP cDNAs. S1 mapping experiments performed with probes covering the 3' end of the two unexpected regions show that three distinct mRNAs correspond to the three cDNAs. Moreover, three peripherin products, two minor 61 and 56 kd products in addition to the major 58 kd peripherin, are observed when poly(A)+ RNA is in vitro translated, the 61 kd peripherin being translated from the 3u-selected RNA. The three RNAs originate from alternative splicing of a unique peripherin gene, thus generating polymorphism of peripherin.
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PMID:Multiple mRNAs encode peripherin, a neuronal intermediate filament protein. 276 51

Peripherin (Formerly the Y protein) is found in the peripheral nervous system. This Triton-insoluble protein is characterized by its isoelectric point (5.6), its apparent molecular weight (56,000 daltons) and its peptide map. Peripherin was also observed in a mouse neuroblastoma cell line, NIE 115, where its expression appeared regulated by the presence of an inducer of morphological differentiation. In order to analyze more precisely this control, the presence of peripherin was investigated in several neuroblastoma cell lines which exhibit different morphological patterns of differentiation and in the rat pheochromocytoma PC 12 cell line. Differentiation of these cells was induced with 1-methylcyclohexane carboxylic acid (CCA) and nerve growth factor (NGF), respectively. Peripherin was found in these different cell lines. Moreover, the cellular amount of peripherin appraised by [35S]-methionine incorporation was significatively increased in differentiated cells. In contrast, other cytoskeletal components did not undergo a similar raise. The level at which the control of the peripherin content takes place was studied in a cell-free translation system. Poly(A)-rich RNAs extracted from growing or differentiated NIE 115 cells directed the synthesis of similar amounts of peripherin in a reticulocyte lysate. In contrast, polysomes prepared from differentiated cells and the corresponding polysomal RNA programmed in vitro the synthesis of twice more peripherin than polysomes or polysomal RNA from growth-phase cells. Since peripherin synthesis is enhanced 5 times in living cells, it seems probable that the cellular amount of peripherin is controlled partly at the translational level and partly at the turn-over level.
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PMID:Regulation of peripherin in mouse neuroblastoma and rat PC 12 pheochromocytoma cell lines. 615 88

Peripherin, a Triton-insoluble protein, whose distribution was found to be restricted to neurons in the rodent and human peripheral nervous system, was characterized by its electrophoretic features (isoelectric point: 5.6; molecular weight: 56,000 daltons) and by its peptidic map after limited proteolysis. Comparative peptide analysis of the 70,000-dalton subunit of neurofilaments (70K NFP), vimentin and peripherin, was performed by two different methods; limited proteolysis with Staphylococcus aureus V8 protease yields a different peptidic map for each protein; treatment with N-chlorosuccinimide, which cleaves preferentially at tryptophan residues, yields only two peptides from each protein: the size of the two fragments indicates that these proteins possess a single tryptophan residue located in the central part of the molecule. A rabbit antiserum raised against mouse peripherin decorated an intracellular filamentous network in mouse neuroblastoma NIE 115 cell line. The IgG fraction of the antiserum recognizes peripherin and the smallest subunit of the neurofilament triplet (70K NFP)--but not vimentin--whereas a monoclonal anti-70K NFP recognizes only the 70K NFP. Moreover, peripherin displays the common antigenic determinant shared by all intermediate filament proteins. Hence, we propose that peripherin represents a new member of the intermediate filament protein family, and might belong to the neurofilament class.
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PMID:Peripherin, a new member of the intermediate filament protein family. 639 22

A series of human neuroblastoma (NB) cell lines was analyzed for expression of peripherin, a class-III intermediate filament protein expressed at high levels in ganglia of the peripheral nervous system. By Western blotting, peripherin protein was detected in all human NB cell lines examined. The highest level of peripherin was found in the NUB-7 cell line, previously characterized as homogeneously neuroblastic. By immunofluorescence labeling, peripherin was shown to be organized in a perinuclear filamentous pattern and, exemplified by IMR32 cells, was also shown to be localized to spontaneously formed neurites. Peripherin was expressed in neuroblastic but not substrate-adherent cells, and was found at low levels in I-type cells. There was a pronounced redistribution of peripherin to neurites formed in response to dibutyryl cyclic adenosine monophosphate (dbcAMP) and all-trans-retinoic acid (RA). In NUB-7 cells, which do not extend neurites in response to nerve growth factor, there was no change in the level of peripherin protein following treatment with this agent. Both dbcAMP and RA induced a redistribution of peripherin to neurite extensions, but only treatment with RA increased the level of the protein as demonstrated with NUB-6A4 and NUB-6C4 subclones. Peripherin was also variably expressed in peripheral neuroepithelioma (NE) cell lines tested, but was organized into a more basket-like filamentous pattern in these cells. The heterogeneous expression and distribution of peripherin in NB and NE cell lines indicate that this protein is associated with maturation of the neuronal phenotype and hence serves as a differentiation marker for tumors derived from the neural crest.
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PMID:Expression and distribution of peripherin protein in human neuroblastoma cell lines. 838 95

The chromatin structure of the mouse peripherin gene domain was analyzed in peripherin-positive and -negative cell lines. At least nine DNase I hypersensitive sites (HSS) are present within the 20-kb peripherin domain in the mouse neuroblastoma cell lines which express peripherin. Three of them are situated in intron I and intron III, the others being distributed within the 5' flanking region up to -5.5 kb. The presence of these sites was also investigated in the peripherin chromatin domain of peripherin-negative cell lines. Two other types of HSS distribution were observed along the peripherin gene according to the category of cell considered: constantly peripherin-negative cells, or negative cells arising from transiently peripherin-expressing precursors. From comparison of HSS patterns in these cell lines with those of neuroblastoma cells, it can be predicted that HSS located in the region -1500/+800 bp participate in cell-specific expression of the mouse peripherin gene.
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PMID:Three different states of the chromatin structure of the mouse peripherin gene. 872 19

We investigated the regulation of the rat neuron-specific enolase gene using a transient transfection approach. Recent transgenic mouse studies have shown that a 1.8-kb segment of the rat NSE gene 5' flanking region, including the first (noncoding) exon but not the first intron, is able to drive expression of a reporter gene in parallel with endogenous NSE. These data suggest that cis-acting elements responsible for the spatial and temporal pattern of NSE gene expression are located within the proximal 1.8 kb of the 5' flanking sequence. To further investigate this region, we joined the 1.8-kb regulatory cassette to the cat reporter gene and generated a number of constructs in which the flanking sequence was progressively deleted from the 5' end. These constructs were tested by transient transfection into neuronal and nonneuronal cells, followed by an assay for CAT activity. We found that as little as 255 bp of 5' flanking sequence was able to confer cell type-specificity on the reporter gene. Further truncation to 120 bp of 5' sequence resulted in a sharp downregulation of reporter activity in PC12 cells but a significant rise in both Neuro-2A neuroblastoma cells and nonneuronal Ltk- cells, indicating that cis-acting elements controlling the regulation of NSE in Ltk-, Neuro-2A, and PC12 cells may lie within the 135 bp region covered by this deletion. This region contains an AP-2 site and an element similar in sequence and position to a motif identified in the proximal promoter region of the neuron-specific peripherin gene. Reduction to 95 bp of 5' sequence resulted in a slight downregulation of CAT activity in all cell lines tested, and further truncation to 65 bp of 5' sequence caused a universal reduction to background levels of CAT activity, concomitant with the disruption of the basal NSE promoter. Our results show that the 5' flanking region of the NSE gene is capable of conferring cell type-specificity on a heterologous gene in transfected cells and that elements responsible for this are located within the proximal 255 bp.
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PMID:Sequences in the proximal 5' flanking region of the rat neuron-specific enolase (NSE) gene are sufficient for cell type-specific reporter gene expression. 906 16


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