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)

To study the regulation of major histocompatibility complex class II antigen by central nervous system cells, the expression of one of these antigens, human leukocyte antigenDR (HLADR) in three human glioblastoma cell lines (HTB14, 16 and 17) and a neuroblastoma cell line (HTB11) was determined. Interferon-gamma (IFN gamma) induced HTB16 and HTB17 cells to express HLADR, and enhanced the antigen expression in HTB14 cells, but it failed to induce HLADR expression in HTB11 cells. Tumor necrosis factor-alpha amplified and accelerated the expression of HLADR induced by IFN gamma in HTB16 cells. Interleukin-1 beta, prostaglandin E2 and transforming growth factor-beta suppressed IFN gamma-induced HLADR expression in HTB16 cells. Several other substances tested did not affect HLADR expression or IFN gamma-induced HLADR. These findings confirm that IFN gamma plays a role in the regulation of HLADR expression in cells derived from the brain and that some other cytokines modify IFN gamma-HLADR interactions.
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PMID:Modulation of human leukocyte antigenDR expression in glioblastoma cells by interferon gamma and other cytokines. 195 63

The expression of NCAM (neural cell adhesion molecule) is precisely regulated in terms of cell type specificity and developmental control. We searched for extracellular factors that may be involved in this regulation using N2A neuroblastoma and NIH 3T3 fibroblastic cells. Factors contained in FBS promoted a two- to threefold increase in NCAM protein and mRNA abundance in both cell lines. This increase in NCAM expression in high serum could be entirely attributed to enhanced levels of the NCAM-140 message. Modulation of NCAM synthesis via an autocrine mechanism is suggested by the observation that medium conditioned by N2A cells stimulated NCAM mRNA expression by 3T3 and N2A cells. Among the pure factors tested, transforming growth factor-beta (TGF beta) was found to act as an inducer of NCAM expression in 3T3 but not in N2A cells. 3T3 cells responded to exposure to TGF beta with a two- to threefold increase in NCAM protein and mRNA. Exposure of early-passage embryonic cells to TGF beta resulted in four- and twofold increases in NCAM protein and mRNA abundance, respectively, suggesting a role for TGF beta in modulating NCAM expression in the embryo. TGF beta seems to act by stimulating the transcriptional activity of the NCAM gene because it did not affect transcript stability and stimulated transcription from a proximal promoter element of the NCAM gene.
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PMID:Modulation of NCAM expression by transforming growth factor-beta, serum, and autocrine factors. 238 Feb 47

In several recent reviews, we have suggested that the mechanism of action of retinoids in controlling cell differentiation is related to their effects on the expression of oncogenes and peptide growth factors. It is currently believed that oncogenes control metabolic pathways that involve peptide growth factors and their receptors, as well as postreceptor signaling mechanisms. Retinoids, therefore, have been valuable probes to study the function of oncogenes and peptide growth factors. In several tumor cells, including human promyelocytic leukemia, human and murine neuroblastoma, and murine teratocarcinoma, retinoic acid induces terminal differentiation, accompanied by suppression of the expression of either the c-myc or the N-myc gene. Many studies have indicated that retinoic acid can markedly increase the number of cellular receptors for epidermal growth factor, which is partially encoded by another oncogene, erb-B. We have shown that retinoic acid greatly inhibits the anchorage-independent growth of a rat fibroblast cell line that has been transfected with the c-myc gene, particularly when these cells are stimulated by the combination of platelet-derived growth factor and transforming growth factor-beta. At present, the mechanisms by which retinoids control oncogene and growth factor expression are unknown. A wide range of new compounds, including the retinoidal benzoic acid derivatives, are now available to study these mechanisms, and will necessitate the identification of a high-affinity receptor for retinoids and the elucidation of the interaction of this receptor with the genome of the cell. The recent synthesis of new terephthalic acid anilides and chalcone carboxylic acid derivatives, which have retinoid-like activity, offers a particularly useful approach to this problem.
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PMID:Mechanism of action of retinoids. 302 29

Melanocytes derived from fetal or adult skin do not propagate in vitro unless cultured in the presence of factors such as 12-O-tetradecanoylphorbol 13-acetate (TPA). In a search for physiological factors regulating the growth of melanocytes, extracts of various cultured cell types were tested. Factors produced by melanoma and astrocytoma cell lines support continued proliferation of melanocytes in the absence of TPA. WI-38, a fibroblast cell line derived from human embryonic lung, was the most active source of melanocyte growth factors. No melanocyte growth-promoting activity was found in extracts of cultured neuroblastoma, renal cancer, normal keratinocytes, or renal epithelium. Nerve growth factor, epidermal growth factor, melanocyte-stimulating hormone, transforming growth factor-beta, and platelet-derived growth factor did not have growth-promoting activity for melanocytes. The presence of melanocyte growth factors and TPA together resulted in the strongest mitogenic activity for melanocytes, permitting the recovery (at 20 days) of 4 to 20 times as many cells as in growth factor or TPA alone.
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PMID:Growth regulation of human melanocytes: mitogenic factors in extracts of melanoma, astrocytoma, and fibroblast cell lines. 402 18

Metastasis in children with neuroblastoma (NB) is a poor prognostic factor despite intensive therapy. In the near future, stem cell factor (SCF) is likely to be used clinically to accelerate bone marrow (BM) recovery after high-dose chemotherapy in patients with advanced NB. The high frequency of BM metastases in NB could be secondary to BM-derived human growth factors (HGF) modulating the adhesion, secondary growth (or both) of circulating metastatic NB cells. To test this hypothesis, we studied the in vitro effects on NB cell lines grown in chemically defined medium of SCF, interleukin (IL)-1 beta, IL-3, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) used alone or in combination. The antigenic expression of NB-associated cell adhesion molecules (CAM) HLA class 1, intercellular CAM-1, neural-CAM and CD44 were assayed by monoclonal antibodies and flow cytometry, and DNA synthesis by 3H-thymidine uptake. The expression of CAM was not modulated by SCF or other HGFs. An increase in thymidine uptake was induced by bFGF alone in IMR-32 cells, while SCF and other HGFs had no notable effect. Our results indicate that SCF and other BM-derived HGFs are unlikely to have a generalised effect on the expression of adhesion molecules by NB cells or proliferation. The clinical administration of recombinant human SCF to children with NB should be safe.
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PMID:Effects of stem cell factor and other bone marrow-derived growth factors on the expression of adhesion molecules and proliferation of human neuroblastoma cells. 757 47

The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.
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PMID:Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins. 827 80

The clotting protease thrombin might contribute to cell damage following brain injury by its ability to retract processes on neurons and astrocytes. Protease nexin-1 (PN-1), a potent inhibitor of thrombin, is localized around cerebral blood vessels where it may protect these cells from extravasated thrombin during injury or alteration of the blood-brain barrier. Here we examined the effects of several injury-related factors on the regulation of PN-1 in cultured brain cells. Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta stimulated the secretion of PN-1 by the neuroblastoma cell line SK-N-SH. This cell line comprises both neuronal and glial cells. Analyses using cloned derivatives of these two cell types showed that PN-1 was secreted by the glial cells; PN-1 secretion was stimulated 90-fold by interleukin-1, 15-fold by tumor necrosis factor-alpha, 10-fold by tumor growth factor-beta, and 4-fold by platelet-derived growth factor. Measurements of newly synthesised PN-1 demonstrated that these factors produced an equivalent stimulation of PN-1 synthesis. The neuronal cells secreted two thrombin-binding proteins distinct from PN-1. Interactions between these two cell types regulated the secretion of PN-1 and the two thrombin-binding proteins.
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PMID:Regulation of protease nexin-1 synthesis and secretion in cultured brain cells by injury-related factors. 842 47

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family of growth factors, was first identified by its ability to promote the survival of midbrain dopaminergic neurons in culture. We demonstrate that GDNF treatment of several neuroblastoma cell lines leads to dose-dependent tyrosine phosphorylation of the RET receptor and that other transforming growth factor-beta family members are not able to activate the RET receptor. GDNF treatment of neuroblastoma cells also results in increased transcription of an Elk luciferase reporter gene, suggesting that GDNF activates the mitogen-activated protein kinase signal transduction pathway.
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PMID:Glial cell line-derived neurotrophic factor signals through the RET receptor and activates mitogen-activated protein kinase. 879 76

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
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PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

Treatment of primary rat embryo hippocampal neuronal cultures with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a 60% decrease in cell viability as determined by MTT incorporation. When these cells were treated with 0.1-10 ng/ml of either transforming growth factor-beta (TGF-beta) 1, 2 or 3 for 24 h before exposure to A beta P, there was a 2.9-, 1.9-, and 3.2-fold increase in cell survival, respectively, compared to cells treated with A beta P alone. The viability of cells treated with A beta P and 0.1-10 ng/ml TGF-beta was comparable to that of cells not treated with A beta P. The protective effects were less pronounced at lower TGF-beta concentrations. The protective effects of pretreatment with TGF-beta were less striking in mouse CCL-N-2a and human SK-N-SH neuroblastoma cell lines. When all cells were treated with TGF-beta for 24 h following a 24 h exposure to A beta P, there was a trend toward increased cell viability which was less significant than pretreatment with TGFs-beta. An isoform-specific TGF-beta SELISA showed that primary hippocampal neuronal cultures and the neuroblastoma cell lines secrete all 3 TGF-beta isoforms. Based on our results, we propose that the increased expression of TGF-beta observed in brains of patients with Alzheimer's disease may offer some degree of neuroprotection.
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PMID:Transforming growth factors-beta protect primary rat hippocampal neuronal cultures from degeneration induced by beta-amyloid peptide. 889 Dec 64


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