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 authors have investigated the relationship between oncogene (N-myc and c-src) expression and major histocompatibility complex (H-2 in the mouse) antigen gene expression at the molecular levels, by using mouse neuroblastoma sublines (NB-1 and NB-V). Fluorescence-activated cell sorter analysis showed that NB-1 cells exhibited positive expression to H-2 Kk, H-2 Dd, and beta-2-microglobulin, while NB-V cells were negative to all three antigens. It was found that dimethyl sulfoxide (DMSO) had a capacity to increase an H-2 class I antigen expression on NB-1 cells, whereas no change was observed on NB-V cells after DMSO treatment. Molecular analysis with deoxyribonucleic and ribonucleic acid (RNA) blot hybridization and immunoprecipitation revealed that the enhancement of H-2 antigen expression on NB-1 cells was modulated at the transcriptional control of the H-2 gene. In contrast, negative H-2 antigen expression on NB-V cells was caused by block at the level of glycosylation of the H-2 heavy chain, although an increase in messenger RNA of the H-2 gene was induced after DMSO treatment. There was neither amplification nor rearrangement of N-myc and c-src oncogenes in either neuroblastoma subline. Nuclear run-on transcription assay revealed that the N-myc gene was post-transcriptionally down-modulated by DMSO, whereas the c-src gene was transcriptionally up-regulated. It was thus suspected that N-myc and c-src might be directly associated with cellular proliferation and differentiation in neuronal tumors and that in vivo tumorigenicity could be regulated by the control mechanism of oncogene expression in relation to H-2 gene expression on tumor cells.
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PMID:[Molecular analysis of relationship between oncogene (N-myc and c-src) expression and major histocompatibility complex antigen gene expression in mouse neuroblastoma lines]. 170 53

Neuroblastoma remains a significant problem in pediatric oncology. Recently a "multidrug-resistance" gene that may cause cells to become resistant to various chemotherapeutic agents has been cloned. The gene encodes the high-molecular-weight plasma membrane protein known as P-glycoprotein. To study the expression of this gene in cells exhibiting the multidrug-resistant phenotype, a panel of sublines selected with several different natural product drugs was established. The drug-sensitive parental BE(2)-C cells were clonally isolated from the human neuroblastoma SK-N-BE(2) line and exhibit a 150-fold increase in the copy number of the N-myc protooncogene. Sublines were selected by stepwise increases in the concentration of actinomycin-D, doxorubicin, vincristine, or colchicine. Gene amplification was assessed using Southern analysis, and RNA levels were determined by Northern and dot-blot analysis. Western blotting was used to determine protein levels. N-myc amplification and expression were simultaneously determined to assess possible alterations associated with development of multidrug resistance. Amplified P-glycoprotein-encoding genes were not seen in control lines but were clearly present in those that had undergone exposure to each of the chemical agents. Similarly, steady-state messenger RNA and protein levels were greatly increased in the drug-resistant sublines. We conclude that human neuroblastoma cells can acquire the multidrug-resistant phenotype after exposure to various chemotherapeutic agents.
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PMID:Multidrug resistance in human neuroblastoma cells. 171 82

Data are presented suggesting that neuroblastoma represents at least two distinct clinical-biologic entities. One, favorable neuroblastoma, is associated with young age and early stage at diagnosis, triploid karyotypes, no 1p abnormalities or N-myc gene amplification, more mature catecholamine synthesis and excretion, and excellent clinical outcome despite no or minimal therapy. The other, unfavorable neuroblastoma, is associated with older age and advanced stage, pseudodiploid karyotypes and 1p deletions, N-myc oncogene amplification, less mature catecholamine synthesis and excretion, and poor outcome despite aggressive multimodality therapy including bone marrow transplantation. Favorable neuroblastomas rarely, if ever, evolve into unfavorable disease. Unresolved issues regarding this hypothesis and implications for the efficacy of preclinical detection through mass screening are discussed.
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PMID:Neuroblastoma represents distinct clinical-biologic entities: a review and perspective from the Quebec Neuroblastoma Screening Project. 172 93

G-banded chromosome analysis of neuroblastoma cells from two children revealed homogeneously staining regions (hsr) in one patient and double minutes (dmin) in the other. Subsequently, both abnormalities were confirmed as areas of N-myc amplification using chromosomal in situ hybridization with a biotinylated N-myc probe. In addition, the first patient's karyotype contained a possible derivative chromosome 17, which was also demonstrated to contain amplified N-myc, indicating the presence of an hsr unidentified by G-banding. Intercellular heterogeneity in the degree of amplification was also identified in the nuclei of interphase cells. This technique provides a quick method for detecting gene amplification, the identification of which may have useful clinical implications.
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PMID:Chromosomal localization of amplified N-myc in neuroblastoma cells using a biotinylated probe. 172 51

Since cadmium exposure results in neuropathological alterations in central nervous system, we investigated the effects of cadmium on the gene expression of neuroblastoma (GOTO) cells. We observed an increase in mRNA levels of heat-shock protein (hsp) 70, hsp 90, hsp 32 and metallothionein after treatment of GOTO cells with cadmium, although the time courses of the changes of individual mRNA of the heat-shock proteins and metallothionein were somewhat different from each other. An accumulation of N-myc and multidrug-resistance gene (MDR1) mRNA was detected in the presence of cadmium. This is contrary to the previous report, in which an inverse correlation between the expression of MDR1 gene and N-myc oncogene in human neuroblastoma had been described. However, the increase of N-myc and MDR1 mRNA in the present study is not likely due to the loss of regulatory mechanism of these genes by cytotoxic effects of cadmium, because active protective mechanisms such as heat-shock proteins and metallothionein could be induced under these conditions.
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PMID:Cadmium causes increases of N-myc and multidrug-resistance gene mRNA in neuroblastoma cells. 175 38

A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5-year-old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1, 10, 19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40- to 80-fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin-labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma.
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PMID:Morphological and cytogenetic characterization and N-myc oncogene analysis of a newly established neuroblastoma cell line. 175 17

Cloning and physical mapping of DNA sequences encompassing N-myc amplicons of a human neuroblastoma cell line were done. A number of lambda phage clones within this region were isolated using the probes prepared by the phenol emulsion reassociation technique. Based on the restriction mapping, they were integrated into 8 contigs with sizes of 25-60 kb which, in total, encompassed a 330 kb region. Several amplicons, 100, 420, 480 and 520 kb in size as a Notl fragment, were identified using hexagonal field gel electrophoresis, and the contigs were assigned in these Notl fragments. The region encompassed by the contigs was equivalent to some 60-80% of the amplicons identified as a Notl fragment. In order to compare the amplified regions flanking the N-myc gene among the cell lines, the phage clones to cover the whole contigs were used for hybridization as a probe. The results showed that the portions of the whole contigs ranging 18-45% were also amplified in the cell lines examined. These results allowed us to identified the 'rearranged sites' which were rather evenly distributed, one at every 40 kb, through the contigs. These observations lead to the idea that an amplified DNA domain is constructed after the multiple rearrangements and then increases in number, finally resulting in the formation of subsets of amplicons with sequence homogeneity.
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PMID:Cloning and physical mapping of DNA sequences encompassing a region in N-myc amplicons of a human neuroblastoma cell line. 176 18

Expression of the proto-oncogenes N-myc and c-myc in the human neuroblastoma cell line, IMR32, was examined after reversible inhibition of DNA synthesis by treatment with deferoxamine. After 48 h treatment with 10(-5) M deferoxamine, the number of c-myc expressing cells doubled, while N-myc expressing cells did not change. The expression level of c-myc in each cell also increased. These results suggested that the synthesis of cellular factor(s) involved in the degradation of c-myc RNA or its product was suppressed by reversible inhibition of cell growth. The regulatory mechanisms of expression of N-myc and c-myc may be distinct.
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PMID:Increased expression of the proto-oncogene, c-myc, in human neuroblastoma cells by reversible inhibition of cell growth. 177 29

We have examined expression of the N-myc, c-fos and smg p25A genes in two human neuroblastoma cell lines during their differentiation. The decrease in the N-myc gene expression and the increase in the c-fos gene expression are observed during the differentiation of NB-1 cells into neuronal cells and of GOTO cells into Schwann-type cells. On the other hand, the smg p25A, a ras p21-like small GTP-binding protein, gene expression is increased in NB-1 cells but not in GOTO cells during their differentiation, suggesting that smg p25A is closely associated with the neuronal phenotype of neuroblastoma cells.
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PMID:Differential expression of the N-myc, c-fos, and smg p25A genes in human neuroblastoma cells during neuronal and Schwannian differentiation. 185 70

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


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