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

The human neuroblastoma cell line CHP100 provides a useful model system in which to study the molecular mechanisms of transcriptional regulation of the low-affinity nerve growth factor receptor (NGFR) gene during neuronal development. Basic fibroblast growth factor (bFGF) induced morphological changes in CHP100 cells, including flattening of cell bodies and neurite outgrowth. bFGF also increased p75NGFR immunoreactivity, as assessed by immunocytochemistry, and increased p75NGFR mRNA levels, as assessed by Northern (RNA) blot analysis. A chimeric gene consisting of 6.7 kb of the 5'-flanking region of the human NGFR gene linked to the chloramphenicol acetyltransferase gene was constructed. In stable transformants of CHP100 cells, 10 ng of bFGF per ml induced an eightfold increase in chloramphenicol acetyltransferase activity. These results indicate that upstream elements of the NGFR gene mediate transcriptional regulation by bFGF.
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PMID:Basic fibroblast growth factor enhances nerve growth factor receptor gene promoter activity in human neuroblastoma cell line CHP100. 131 50

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 nerve growth factor (NGF) receptor (NGFR) cDNA was transfected into a neuroblastoma cell line (HTLA 230) which does not express a functional NGF-NGFR signal transduction cascade. Short-term treatment of stably transfected cells (98-3) expressing membrane-bound NGF receptor molecules resulted in a cell cycle-dependent, transient expression of the c-fos gene upon treatment with NGF, suggesting the presence of functional high-affinity NGFR. Extensive outgrowth of neurites and cessation of DNA synthesis occurred in transfectants grown on an extracellular matrix after long-term treatment with NGF, suggesting terminal differentiation. Our data support the idea that introduction of a constitutively expressed NGFR cDNA into cells with neuronal background results in the assembly of a functional NGF-NGFR signal cascade in a permissive extracellular environment.
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PMID:Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA. 216 46

A trypsin-degradable nerve growth factor (NGF) receptor associated with the phospholipid component of the surface membrane has been detected on F98 anaplastic glioma cells. NGF also bound to the nucleus of F98 cells. Bound NGF was not displaceable by insulin, cytochrome C, growth hormone, or bovine serum albumin. Specific binding of NGF occurred with a Kd of 8.79 X 10(-12) M as determined by Scatchard analysis with approximately 34,000 receptors per cell. Specific NGF binding was also evident to C6 rat glioma cells and IMR-32 human neuroblastoma cells, but not to 3T3 mouse fibroblasts. These observations coupled with previous findings suggest that the NGF receptor may be a marker found on cells of neural derivation. As little as 1 ng/ml NGF caused an increase in the adhesiveness of F98 cells to culture flasks. Increased adhesiveness could be observed in as little as 5 min and was apparent for at least 45 min. At 25 min in NGF-containing medium, 24 +/- 3% of the cells adhered to the flasks compared to 13 +/- 1% of control cells. The NGF-induced increase in adhesiveness was not duplicated by epidermal growth factor, insulin, cytochrome c, bovine serum albumin, dibutyryl cyclic AMP, or sodium butyrate. Oxidized NGF blocked the effect of native NGF, but had little or no adhesion-promoting activity itself. Pretreatment of the cells with NGF was also effective in promoting adhesion, even though nerve growth factor was not added to the binding medium. The effect of this pretreatment was reversible; when NGF-pretreated cells were grown in medium without supplemental NGF, the adhesiveness of the cells returned to control levels or lower.
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PMID:Increased adhesion response of anaplastic glioma cells to nerve growth factor and the presence of specific receptors. 631 24

The expression of low-affinity nerve growth factor receptor (NGF-R) by primitive neuroectodermal tumors (PNETs) was analyzed in vivo and in vitro to investigate the relationship between NGF-R expression and cellular differentiation. NGF-R was expressed in one medulloblastoma cell line and two neuroblastoma cell lines. When these cells were induced to differentiate by treatment with dibutyryl cyclic adenosine monophosphate, NGF-R was overexpressed and there was increased expression of neurofilament proteins. Immunohistochemistry investigation of tumor tissues demonstrated that NGF-R was expressed by a subset of PNETs with a neuronal phenotype marked by neurofilament protein expression, but not by gliomas and PNETs without a neuronal phenotype. Growth inhibition assay demonstrated that NGF inhibited the growth of cells expressing NGF-R. These results indicate that NGF-R expression is a useful marker of neuronal differentiation by PNETs.
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PMID:Expression of nerve growth factor receptor by human primitive neuroectodermal tumors. 752 37

Growth factors can induce both proliferation or differentiation of neuroblastoma (NB) cells through interaction with specific receptors. Using two automated colorimetric assays for determinations of cell numbers, the present study demonstrates that a) different NB and neuroepithelioma cell lines show distinct responses, both qualitatively and quantitatively, to basic FGF (bFGF), NGF, and EGF; b) even closely related NB cell lines (e.g., SK-N-SH, SH-SY5Y, and SHEP) do not respond uniformly to these factors; c) responses of the two neuroepithelioma cell lines employed (SK-N-MC and CHP-100) differ, but match those of certain NB cell lines; and d) two growth factors, bFGF and EGF, may both stimulate or inhibit proliferation, depending on the cell line studied. Specifically, IMR-32, SK-N-SH, and SH-SY5Y showed a mitogenic response to each growth factor. Maximal proliferative responses ranged from 204-355% as compared to controls (100%). GICAN was stimulated by NGF (199%), and SK-N-MC and NMB by EGF (282 and 140%, respectively), but other factors were ineffective. CHP-100 and GIMEN were inhibited by bFGF. NGF and EGF were not effective on CHP-100 cells, while EGF caused an arrest of mitogenic activity in GIMEN cells, and NGF stimulated their proliferation. Cell lines SHEP and LAN1 did not respond to any factor. To begin to analyze putative relationships of growth factor responsiveness and growth factor/growth factor receptor expressions, IMR-32, GIMEN, and LAN1 cell lines were studied for the presence of bFGF, NGF, FGF receptors (R)-1 (flg) and FGFR-4, trk, and low-affinity NGF receptor (p75) mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterogeneity of human neuroblastoma cell lines in their proliferative responses to basic FGF, NGF, and EGF: correlation with expression of growth factors and growth factor receptors. 762 87

Four children with advanced or relapsed neuroblastoma were treated with oral 13-cis-retinoic acid 0.75 mg/kg/day. Clinical response to retinoic acid was noted only in the two children with tumors coexpressing trk protooncogene mRNA, encoding an essential part of the nerve growth factor (NGF) high affinity receptor, and low affinity NGF receptor gene (LNGFR) mRNA. Clinical stage or age, plasma neuropeptide Y, tumor DNA ploidy and N-myc amplification did not as accurately predict response to retinoic acid as NGF receptor mRNAs. In vitro data have shown that retinoic acid up regulates LNGFR expression and NGF sensitivity via interaction with specific regulatory elements in the LNGFR gene promoter. We hypothesize that part of the therapeutic effect of retinoic acid in neuroblastoma in vivo may be exerted via increased NGF receptor expression and NGF sensitivity. Analysis of trk and LNGFR mRNA may be useful to predict clinical response to retinoic acid in these children.
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PMID:Expression of nerve growth factor receptor mRNAs and clinical response to retinoic acid in neuroblastoma. 797 6

Information on the transmembrane signaling events and subsequent biochemical processes initiated by ciliary neurotrophic factor (CNTF) receptor activation in neurons is lacking. SH-SY5Y cells, a human neuroblastoma cell line expressing CNTF receptors, were used to study metabolic changes associated with functional ligand-receptor interactions. Real-time measurements quantifying the rate of extracellular acidification by SH-SY5Y cells (a measure of metabolic activity) were made using a silicon-based cytosensor. Application of recombinant human CNTF (rhCNTF) to resting SH-SY5Y cells increased their acidification rate in a concentration and time-dependent manner with an apparent EC50 of 60 ng/ml. Pretreatment of cells with phosphatidylinositol-specific phospholipase C (PI-PLC) prevented the CNTF, but not an NGF-stimulated increase in acidification rate. Collectively, these results demonstrate that: (1) SH-SY5Y cells express functional CNTF receptors; and (2) the initial signal transduction mechanism activated by the CNTF receptor in SH-SY5Y cells is distinct from that activated by the NGF receptor; however, both may ultimately stimulate the same downstream biochemical messengers to increase cellular metabolism.
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PMID:Recombinant human ciliary neurotrophic factor stimulates the metabolic activity of SH-SY5Y cells as measured by a cytosensor microphysiometer. 806 84

The human trkA cDNA was transfected into a malignant human neuroblastoma (NB) cell line (HTLA230) to investigate its role in NB growth and differentiation. This cell line lacks expression of both endogenous trkA and gp75NGFR genes. Transfectants expressing the trkA mRNA and surface-bound receptors transcriptionally activate immediate-early genes (c-fos, c-jun, and jun-B) following nerve growth factor (NGF) stimulation. NGF treatment induces growth arrest as well as down-regulation of the amplified N-myc oncogene. Genes selectively expressed in mature neurons (SCG-10, ret proto-oncogene, GAP-43, etc.) are transcriptionally activated, and neurite outgrowth further demonstrates differentiation of transfectants following NGF stimulation. trkA-expressing NB cells remain tumorigenic in nude mice; however, subcutaneous treatment of tumor-bearing mice with NGF induces Schwannian and neuronal cell differentiation similar to the induction seen in human ganglioneuroblastomas. Thus, trkA expression in HTLA230 cells is sufficient to generate a functional NGF receptor complex that leads to growth-arrested and differentiated NB cells in vitro and in vivo in the presence of NGF. Hence, NGF may play a crucial role in NB cell differentiation and regression in vivo.
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PMID:Expression of trkA cDNA in neuroblastomas mediates differentiation in vitro and in vivo. 824 62

Neocarzinostatin is an antineoplastic agent that induces differentiated morphology in human (SK-N-SH) neuroblastoma cells in culture. We have compared this morphological differentiation with that induced by the endogenous differentiation inducer, nerve growth factor (NGF), and have explored the effects of exposure to NGF upon the morphological changes induced by neocarzinostatin in SK-N-SH cells. Both NGF and neocarzinostatin induced process outgrowth in these cells. The processes formed in the presence of NGF however, were shorter and thinner than those induced by neocarzinostatin. Furthermore, only neocarzinostatin induced enlargement of the somata of the cells, and caused cell death in a concentration-dependent fraction of the culture. These distinguishing features of treated cells allowed us to determine whether or not NGF exposure altered responsiveness of the cells to neocarzinostatin. NGF (100-1000 ng/mL) protected SK-N-SH cells from the morphological and cytocidal effects of neocarzinostatin (1-hr exposure, 0.017 to 0.033 micrograms/mL). Protection from neocarzinostatin required that NGF be continuously present for a period beginning 24 hr prior to neocarzinostatin exposure and continuing for the duration of the experiment, implying that the protection afforded by NGF has a latency necessitating pretreatment, and is reversible. These results suggest that neocarzinostatin is taken up by the cells and can exert its effects once NGF is removed, even after neocarzinostatin is washed out of the medium. The signal transduction cascade triggered by NGF receptor binding may prevent the action of neocarzinostatin or the expression of the cellular changes induced in SK-N-SH cells by neocarzinostatin.
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PMID:Prevention of neocarzinostatin-induced cell death and morphologic change in SK-N-SH human neuroblastoma cells by continuous exposure to nerve growth factor. 836 46


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