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)

Retinoic acid is a naturally occurring metabolite of vitamin A that influences the differentiation of a variety of neural cells in vitro. In the LA-N-1 human neuroblastoma line, retinoic acid treatment increases the binding of nerve growth factor (Bmax). The purpose of this study was to examine the effects of retinoic acid on PC12 rat pheochromocytoma, a neural crest-derived cell line that can be induced to express a sympathetic neuroblast-like phenotype by nerve growth factor treatment. In contrast to the differentiating effects of nerve growth factor, retinoic acid treatment of PC12 cells had a negligible effect on cellular morphology. However, treatment with retinoic acid enhanced the survival of PC12 cells following oxidative injury generated by H2O2 treatment in a manner that is qualitatively similar to that observed after nerve growth factor treatment. Also, there was an increase in 125I-nerve growth factor binding activity in solubilized PC12 membrane preparations derived from retinoic acid-treated PC12 cells. These data suggest that retinoic acid may play a role in neuronal development and in neuronal injury by stimulating the ability of neurons to cope with oxidative stress and/or by enhancing neuronal responsiveness to trophic factors such as the nerve growth factor.
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PMID:Antioxidant effect of retinoic acid on PC12 rat pheochromocytoma. 164 45

Neuroblastoma cell lines and tumors are characterized by low HLA class I expression. The majority of neuroblastoma cell lines and a high percentage of disseminated tumors display amplification of the nuclear protooncogene N-myc. An inverse correlation between HLA class I expression and N-myc amplification and overexpression has been recently described in neuroblastomas (NBs). In this study we have shown that cytokines (recombinant gamma-interferon, recombinant alpha-tumor necrosis factor), differentiation agents (dibutyryl cyclic AMP, phorbol myristate acetate) and growth factors (nerve growth factor, epithelial growth factor) were able to influence the growth rate and surface expression of HLA class I molecules as well as of a tumor-associated antigen on 2 representative NB cell lines. Induced decreased growth rate in NB cells was not always related to decreased N-myc expression. Analysis at the mRNA level revealed that both N-myc and HLA class I RNA steady-state levels could be modulated by several substances, including recombinant gamma-interferon, phorbol myristate acetate, dibutyryl cyclic AMP, and epithelial growth factor and were not necessarily linked. An inverse correlation between N-myc and HLA mRNA levels was observed only after exposure of NB cells to recombinant alpha-tumor necrosis factor. We conclude that N-myc and HLA class I RNA steady-state levels can be modulated independently and suggest that they are not necessarily inversely regulated.
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PMID:In vitro modulation and relationship between N-myc and HLA class I RNA steady-state levels in human neuroblastoma cells. 170 47

The bcl2 protooncogene was originally discovered because of its involvement in t(14;18) chromosomal translocations frequently found in non-Hodgkin's lymphomas. The expression of this gene is reported to be highly tissue specific, with bcl2 mRNAs being readily detectable only in hematolymphoid tissues and brain. To explore the possible involvement of bcl2 in neural tumors, we surveyed a variety of tumor cell lines for the presence of the p26-BCL2 protein by immunoprecipitation and immunoblotting methods. Very high levels of BCL2 protein were found in three of nine neuroblastoma (NB) cell lines examined; these levels of p26-BCL2 were comparable to lymphoma cell lines that contain a t(14;18). Despite the impressive relative amounts of BCL2 protein, however, no structural alterations or changes in the methylation status of bcl2 genes were detected in these NB cell lines by conventional Southern blotting. Of the other NB cell lines surveyed, three contained intermediate levels of BCL2 and another three cell lines had little or no detectable BCL2 protein, raising the possibility that determination of relative levels of BCL2 protein may help to segregate neuroblastomas into groups with different biological and clinical characteristics. BCL2 protein levels were not influenced by induction of neuronal differentiation with nerve growth factor in two of the two cell lines examined [SH-SY5Y (high BCL2); GICAN (low BCL2)] and did not correlate with N-MYC gene amplification or expression of nerve growth factor receptors. NB cell lines that contained little or no detectable BCL2 protein, however, tended to contain significant proportions of flat epithelioid cells, whereas bcl2-expressing cell lines were composed primarily of neuronal-like cells, suggesting that expression of this protooncogene correlates with the differentiation characteristics of these tumor cell lines. In addition to NBs, lower levels of BCL2 protein were also found in a variety of other neural crest-derived tumors and tumor cell lines, including some neuroepitheliomas, Ewing's sarcomas, neurofibromas, and melanomas. With regard to tumors of central nervous system origin, bcl2 expression was absent from most medulloblastomas but was detected at moderate to low levels in a retinoblastoma and some glioblastoma multiforme cell lines. Taken together, these findings imply that bcl2 protooncogene expression is differentially regulated within the various lineages of cells that give rise to the nervous system.
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PMID:Differential expression of bcl2 protooncogene in neuroblastoma and other human tumor cell lines of neural origin. 174 26

The antineoplastic drug 4'-iodo-4'-deoxydoxorubicin (IDX), a new halogenated anthracycline (1), was examined as a differentiation inducing agent on the human neuroblastoma cell lines TS12 and SK-N-MC. IDX induced morphological and biochemical differentiation and growth inhibition. The effect of a combined treatment of IDX with retinoic acid (RA) and with nerve growth factor (NGF) respectively was then investigated. The responses of neuroblastoma cells to IDX alone and to these combined treatments were compared, with respect to neuritic outgrowth, acetylcholinesterase activity and cellular growth. The data obtained indicate that the combination of differentiation-inducing drugs may be able to enhance the effects of the same drugs given alone.
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PMID:Neuronal cell differentiation of human neuroblastoma cells by inducing agents in combination. 176 60

Retinoic acid (RA) is known to induce differentiation of neuroblastoma cells in vitro. Here we show that treatment of two human neuroblastoma cell lines, SY5Y and IMR32, with RA resulted in a fivefold increase of the integrin alpha 1/beta 1 expression. The effect was selective because expression of the alpha 3/beta 1 integrin, also present in these cells, was not increased. The up-regulation of the alpha 1/beta 1 differentiated SY5Y cells correlated with increased neurite response to laminin. In fact, RA-treated SY5Y cells elongated neurites on laminin-coated substratum more efficiently compared with untreated cells or cells treated with nerve growth factor, insulin, or phorbol 12-myristate 13-acetate. These three agents induced partial morphological differentiation but did not increase alpha 1 integrin expression. Neurite extension in RA-treated cells was more efficient on laminin than on fibronectin or collagen type I and was inhibited with beta 1 integrin antibodies on all three substrates. Affinity chromatography experiments showed that alpha 1/beta 1 is the major laminin receptor in both untreated and RA-treated SY5Y cells. These data show that RA, a naturally occurring morphogen implicated in embryonic development, can selectively regulate the expression of integrin complexes in neuronal cells and suggest an important role of the alpha 1/beta 1 laminin receptor in the morphological differentiation of nerve cells.
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PMID:Up-regulation of the integrin alpha 1/beta 1 in human neuroblastoma cells differentiated by retinoic acid: correlation with increased neurite outgrowth response to laminin. 183 59

In earlier studies, a 75,000-dalton glycoprotein (gp75) has been identified as a component of both low- and high-affinity nerve growth factor (NGF) receptors (NGFRs). Using an amphoteric expression vector, we have introduced the cDNA encoding the human gp75 into two neuroblastoma cell lines. SHEP is a human neuroblastoma cell line that lacks most neuronal characteristics and does not express NGFRs. The transformant line SHEP/NGFR expressed a single affinity class of NGF binding sites, did not display NGF-induced up-regulation of fos oncogene expression, and did not efficiently internalize NGF. LAN5 is a neuroblastoma cell line with neuronal characteristics, including expression of neurofilament and display of short neurites. This cell line expresses a small number of high-affinity NGFRs but no detectable low-affinity sites. The transformant line LAN5/NGFR expressed both high- and low-affinity NGFRs, displayed NGF-induced up-regulation of fos oncogene, and efficiently internalized NGF. The number of high-affinity NGF binding sites was nearly the same for LAN5 and LAN5/NGFR, a finding suggesting that there is a limiting number of some separately coded factor or subunit that is required for high-affinity NGFRs. Because NGF induction of fos oncogene expression correlated with expression of high-affinity NGFRs, the putative second factor may also limit NGF responsiveness.
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PMID:Characterization of two neuroblastoma cell lines expressing recombinant nerve growth factor receptors. 184 77

The in situ C-1300 murine neuroblastoma (MNB) tumor model was used to investigate the influence of exogenously administered nerve growth factor (NGF) on tumor growth and tissue catecholamine concentration in mice sympathectomized with 6-hydroxy-dopamine (6-OHDA) on postnatal days 4-10. Mice were implanted with 1 x 10(6) disaggregated MNB cells 3 days after termination of 6-OHDA administration. NGF (12-15 micrograms/mouse/day) treatment was initiated at the time of MNB cell implantation and continued until sacrifice of the animal. The time interval between tumor cell implantation and detection of palpable tumor (tumor onset time), transverse tumor diameter, tumor weight, tumor weight to body weight ratio, and tumor catecholamine concentration were determined. Neonatal sympathectomy caused a decrease in myocardial norepinephrine concentration of 88% compared with vehicle-treated animals as well as a significant reduction in total body and organ weight. Average body, brain, heart, and spleen weights were decreased 31%, 16%, 25%, and 42%, respectively, below control values. The daily injection of NGF, from the time of MNB tumor implantation to sacrifice, did not prevent these effects of chemical sympathectomy from being expressed. Tumor onset time following implantation of MNB cells was significantly increased in neonatally sympathectomized mice and was not altered by treatment with NGF. In contrast, the decrease in MNB tumor growth rate observed in sympathectomized mice was reversed by administration of NGF. Mean tumor weight and mean tumor to body weight ratio were 89% and 115% of comparable control values, respectively, in sympathectomized mice receiving exogenous NGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nerve growth factor on C-1300 murine neuroblastoma tumor growth and catecholamine content in neonatally sympathectomized mice. 190 44

Two kinds of novel neural trophic factors were currently detected in von Recklinghausen neurofibroma (NF1) extracts. One of the two was a growth factor, neuroblastoma growth factor (Mr less than 5 kDa), which promotes the proliferation of human neuroblastoma cell and survival and neurite-extension of rat cortical neurons, but differently from nerve growth factor (NGF) or NGF-like factors. The other one was a glial growth inhibitor (Mr = 100 kDa), which suppresses the growth of glioma cell lines, astrocytoma, glioblastoma, oligodendroglioma and Schwannoma. These factors do not appear to be previously identified cytokines or growth factors such as interleukins, granulocyte colony-stimulating factor, NGF and fibroblast growth factor. There was also detectable ciliary neurotrophic factor-like activity in the extracts. The primary cause of high contents of these factors in NF1 is not known, but may relate to fundamental mechanisms controlling growth and differentiation of neurons and glias during development of nervous system.
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PMID:von Recklinghausen neurofibroma produces neuronal and glial growth-modulating factors. 193 68

Neuroblastoma is a tumor of postganglionic sympathetic origin, and nerve growth factor (NGF) is normally required for the survival and differentiation of sympathetic neuroblasts. Since the biological activity of NGF is mediated by the NGF receptor (NGFR), we hypothesized that defects in the NGF/NGFR pathway may play a role in maintenance of the undifferentiated state of neuroblastomas. To test this hypothesis, we examined the structure of the NGFR at the DNA, RNA, and protein levels in a panel of 10 neuroblastoma cell lines. In addition, we examined the function of the NGFR in these lines by analysis of NGF binding kinetics, as well as by the ability of NGF to induce c-fos expression and neurite outgrowth. Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes. Northern blot and ligand binding/immunoprecipitation assays revealed four receptor-positive cell lines (NGP, NLF, SK-N-SH, and LA-N-6), with NGFR mRNA and protein of expected sizes (3.8 kilobases and Mr approximately 75,000, respectively). NGF binding assays and Scatchard analyses were performed on the four NGFR-positive lines. The NGP line possesses only low-affinity receptor (Kd approximately 3.5 x 10(-9)), whereas the other three lines express both low- and high-affinity forms (Kd approximately 10(-9) and Kd approximately 10(-11), respectively). However, none of the 10 lines exhibited a response to NGF treatment as assayed by c-fos mRNA induction and neurite extension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple defects of the nerve growth factor receptor in human neuroblastomas. 196 76

Human neuroblastoma SK-N-SH-SY5Y (SY5Y) and rat pheochromocytoma PC12 cells are model cell lines used in the study of nerve growth factor (NGF) effect. The effects of NGF are initiated by binding to cell surface receptors (NGFR). The amino acid sequence for NGFR has been deduced based on the identification of a single gene for NGFR. However, there are two kinds of NGF binding activities and several reported molecular weights of NGFR. We report here on the demonstration of NGFR-like proteins from PC12 and SY5Y cells by sequential lectin chromatography, reverse-phase HPLC, and SDS-PAGE analysis of immunoprecipitates obtained with NGFR-specific monoclonal antibodies. For both human and rodent NGFR, there was a tendency for the higher molecular-weight species of NGFR-like proteins to be eluted in more hydrophobic fractions. Also, the expression of different species of NGFR could be modified by treatment with retinoic acid (RA). These results are consistent with the hypothesis that the different molecular species of NGFR may result from the generation of a truncated form of NGFR, the presence of sugar residues on the NGFR protein, dimer formation between NGFR, or the association of NGFR with a receptor-associated protein.
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PMID:Reverse-phase high-performance liquid chromatography of nerve growth factor receptor-like proteins identified with monoclonal antibodies. 196 79


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