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

B104 neuroblastoma cells are excitable, but the ion channels underlying electrogenesis in these cells have not been identified. RT-PCR, restriction enzyme analysis and in situ hybridization were used to study sodium channel mRNAs in B104 cells. High levels of sodium channel alpha-subunit mRNAs III, NaG and Na6 and beta 1-subunit mRNA were detected by RT-PCR in B104 cells. Low levels of types I and II alpha-subunit mRNAs were also present. In situ hybridization with subtype-specific riboprobes detected sodium channel alpha-subunit mRNAs III, NaG and Na6 and beta 1-subunit mRNA in B104 cells; analysis of the percentage of B104 cells expressing each alpha-subunit mRNA subtype suggests that some cells express the mRNAs for several alpha-subunits.
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PMID:Sodium channel mRNA in the B104 neuroblastoma cell line. 879 8

Laminin (Ln) isoforms may play important roles in neuronal development, particularly axon guidance, but neural receptors mediating interactions with Ln are not entirely understood. In this paper, we have compared the adhesive and process outgrowth activities of a human neuroblastoma cell line SY5Y on various laminin isoforms. Cell adhesion and process outgrowth were examined on murine Ln-1 (Englebreth-Holm-Swarm sarcoma laminin), human placental Ln-1 (human Ln-1[p]), human Ln-2 (merosin), human Ln-5 (kalinin/epiligrin/nicein), and human foreskin keratinocyte extracellular matrix extract (human HFK-ECM). Ln-5 was shown to evoke process outgrowth in amounts comparable to other Ln isoforms. Antibody perturbation experiments showed that adhesion and process outgrowth on murine Ln-1 was primarily mediated by the integrin alpha 1 beta 1, whereas adhesion and outgrowth on human Ln-5 and human HFK-ECM were mediated by alpha 3 beta 1. Adhesion to human Ln-1(p) and Ln-2 was not blocked by addition of anti-alpha 1 or anti-alpha 3 antibodies alone, but adhesion was partially perturbed when these antibodies were added in combination. Process outgrowth on human Ln-1(p) was blocked when either anti-alpha 3 or anti-beta 1 antibodies were added, indicating that alpha 3 beta 1 is the primary integrin heterodimer responsible for process extension on this substrate. These results demonstrate that Ln-5 and other Ln isoforms support comparable levels of adhesion and process outgrowth, but different integrin heterodimers, alone and in combination, are used by SY5Y cells to mediate responses.
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PMID:Human SY5Y neuroblastoma cell interactions with laminin isoforms: neurite outgrowth on laminin-5 is mediated by integrin alpha 3 beta 1. 880 89

In this study we have determined the binding specificities of four different neuronal cell types to tenascin-C (TN-C) and laminin using a cell adhesion assay. TN-C was repulsive for small cerebellar neurons and PC12 phaeochromocytoma cells, since after short-term adhesion to the substrate-bound molecule with a maximum of cell binding at 45 min, the cells detached from the substrate and after 22 h only about 25% of the originally adherent cells were still bound. For N2A neuroblastoma cells and retinal cells TN-C was an adhesive substrate, since the number of adherent cells did not decrease after the initial attachment period. All four cell types adhered well to laminin at all time points studied. For short-term adhesion of small cerebellar neurons and PC12 cells two binding sites were identified on TN-C, one being localized within the epidermal growth factor-like repeats three to five and the second within fibronectin type III-like repeats three and four. One binding site for N2A and retinal cells was localized within fibronectin type III-like repeat seven. Binding of small cerebellar neurons to TN-C was dependent on Ca2+, but not on Mg2+ and was inhibitable by polyclonal antibodies to beta 1 integrin. Short-term adhesion of small cerebellar neurons was also inhibitable with a mixture of recombinant fragments of TN-C encompassing the whole molecule, although the specific inhibitory activity of this mixture was ten-fold lower on a molar basis when compared to the native molecule. Our observations indicate that different neuronal cell types use distinct binding sites on TN-C for repellent or adhesive interactions and that beta 1 integrin is involved in the recognition event leading to repulsion of small cerebellar neurons.
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PMID:Distinct sites on tenascin-C mediate repellent or adhesive interactions with different neuronal cell types. 882 Oct 32

IMR32, a neuroblastoma cell line, and CADO LC6, a small cell lung cancer (SCLC) cell line, extended neurite-like processes when cultured on fibronectin (FN)-coated surfaces or cultured in a serum-free medium. Monoclonal antibodies against the integrin beta 1 subunit inhibited this process formation, suggesting that their morphological change is initiated by beta 1 integrin-dependent signal transduction to the cell interior. Anti-phosphorylation level of a 100-kDa protein, but not 125-kDa focal adhesion kindase, correlated well with the morphological change in both cell lines. This 100-kDa protein phosphorylation did not accompany FN-induced morphological changes in NIH 3T3 fibroblasts or A549 adenocarcinoma cells. These findings suggest that neuroblastoma and SCLC may share beta 1 integrin-mediated signaling events distinct from nonneuronal cells.
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PMID:A 100-kDa protein tyrosine phosphorylation is concurrent with beta 1 integrin-mediated morphological differentiation in neuroblastoma and small cell lung cancer cells. 883 61

The thyrotropin-releasing hormone (TRH) gene is regulated negatively at the transcriptional level by thyroid hormone (T3). T3 positive regulatory effects on other target genes, such as the growth hormone gene, are mediated through heterodimerization of thyroid hormone receptors (TRs) with RXR or other auxiliary nuclear protein(s). To explore whether an accessory co-suppressor protein(s) may be involved in T3 inhibitory regulation of human TRH gene transcription, transient gene expression studies have been carried out using a hTRH-luciferase (TRH-Luc) chimetric reporter construct, an hTR beta 1 expression construct, and pABgal-hTR beta 1 ligand-binding domain (LBD) fusion constructs, cotransfected into a human neuroblastoma cell line (HTB-11,ATCC). Results herein indicate that T3-dependent inhibitory regulation (48-60% of control) of the hTRH gene promoter by hTR beta 1-T3 complexes could be abrogated completely by cotransfection of a 10 x excess of hTR beta 1-LBD (TR 168-456 aa) in a pABgal94 vector. In striking contrast, cotransfection of a 10 x excess of highly truncated hTR beta 1-LBD (TR 452-456 aa) failed to reverse T3-mediated TRH promoter inhibition. This squelching effect by excessive intact TR-LBD, moreover, could not be reversed by raising T3 concentration 100-fold (from 10(-8) to 10(-6) M), thus excluding a squelching effect of T3 itself by excess LBD. These results suggest that negative regulation of the hTRH gene promoter activity by TR beta 1-T3 complexes involves interactions with an accessory co-suppressor protein, which may bridge DNA-bound TR beta 1-T3 complexes to the transcriptional initiation complex.
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PMID:Reversal of TR-T3 inhibition of the hTRH gene by excess TR ligand-binding domain: evidence for novel accessory protein. 883 32

We describe here a novel monoclonal antibody (mab H6) which recognizes CD9, an integral cell surface constituent previously described in cells of the hematopoietic lineage and involved in the aggregation of platelets. Mab H6 was raised against membranes of immature mouse astrocytes and reacted with a protein of 25-27 kD in detergent extracts of adult mouse brain membranes. Sequence analysis of the N-terminal amino acids revealed an identity of 96% with CD9 from mouse kidney. CD9 was localized in the central and peripheral mouse nervous systems: in the spinal cord of 11-day-old mouse embryos, CD9 was strongly expressed in the floor and roof plates. In the adult mouse sciatic nerve, myelin sheaths were highly CD9-immunoreactive. Mab H6 reacted with the cell surfaces of both glial cells and neurons in culture and inhibited migration of neuronal cell bodies, neurite fasciculation and outgrowth of astrocytic processes from cerebellar microexplants. Neurite outgrowth from isolated small cerebellar neurons was increased in the presence of mab H6 on substrate-coated laminin, but not on substrate-coated poly-L-lysine. Addition of mab H6 elicited an increase in intracellular Ca2+ concentration in these cells on substrate-coated laminin. Immunoprecipitates of CD9 from cultured mouse neuroblastoma N2A cells contained the alpha 6/beta 1 integrin. Moreover, preparations of CD9 immunoaffinity-purified from adult mouse brain using a mab H6 column contained the neural adhesion molecule L1, but not other neural adhesion molecules. CD9 bound to L1, but not to NCAM or MAG. Both the alpha 6/beta 1 integrin and L1 could be induced to coredistribute with CD9 on the surface of cultured neuroblastoma N2A cells. The combined observations suggest that CD9 can associate with L1 and alpha 6/beta 1 integrin to influence neural cell interactions in vitro.
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PMID:CD9 of mouse brain is implicated in neurite outgrowth and cell migration in vitro and is associated with the alpha 6/beta 1 integrin and the neural adhesion molecule L1. 883 70

The mouse Sia alpha 2,3Gal beta 1, 4GalNAc alpha 2,8-sialyltransferase (ST8Sia III) genomic gene, whose transcripts are only expressed in fetal and newborn brain and testis, was isolated and its 5'-flanking region was analyzed. The gene was found to span about 8 kb and to be composed of only four exons. The genomic ST8Sia III gene is much smaller and its organization much simpler than other sialyltransferase genes so far reported, which span more than 25 kb and comprise seven or more exons. In particular, the sialyl motif L of ST8Sia III, which is a highly conserved region in all cloned sialyltransferases, was in one exon. In contrast, this motif is encoded by discrete exons in the other sialyltransferases. The ST8Sia III gene was highly expressed in the mouse brain and gave rise to at least three transcripts (2.1 kb, 2.4 kb, and 6.5 kb), which differed in the length of their 3'-untranslated regions through the alternative use of different polyadenylation sites. Primer extension and S1 nuclease protection analyses of mRNA prepared from newborn brain revealed that ST8Sia III gene expression started from a unique site at 382 nt upstream of ATG. Although the promoter region lacked an apparent TATA or CCAAT box and potential regulatory motifs, a transfection experiment involving neuroblastoma cells expressing ST8Sia III demonstrated the minimal promoter activity exhibited by the proximal region 418 bp upstream from the ATG codon, which suggests the presence of tissue-specific enhancer elements.
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PMID:Unique genomic structure and expression of the mouse alpha 2,8-sialyltransferase (ST8Sia III) gene. 892 52

Nicotinic acetylcholine receptors (nAChR) are diverse members of the ligand-gated ion channel superfamily of neurotransmitter receptors and play critical roles in chemical signaling throughout the nervous system. Reports of effects of substance P (SP) on nAChR function prompted us to investigate interactions between several tachykinins and human nAChR subtypes using clonal cell lines as simple experimental models. Acute exposure to SP inhibits carbamylcholine- or nicotine-stimulated function measured using 86Rb+ efflux assays of human ganglionic (alpha 3 beta 4) nAChR expressed in SH-SY5Y neuroblastoma cells (IC50 approximately 2.3 microM) or of human muscle-type (alpha 1 beta 1 gamma delta) nAChR expressed in TE671/RD clonal cells (IC50 approximately 21 microM). SP also acutely blocks function of rat ganglionic nAChR expressed in PC12 pheochromocytoma cells (IC50 approximately 2.1 microM). Neurokinin A and eledoisin inhibit function (extrapolated IC50 values between 60 and 160 microM) of human muscle-type or ganglionic nAChR, but neurokinin B does not, and neither human nAChR is as sensitive as PC12 cell alpha 3 beta 4-nAChR to eledoisin or neurokinin A inhibition. At concentrations that produce blockade of nAChR function, SP fails to affect binding of [3H]acetylcholine to human muscle-type or ganglionic nAChR. SP-mediated blockade of rat or human ganglionic nAChR function is insurmountable by increasing agonist concentrations. Collectively, these results indicate that tachykinins act noncompetitively to inhibit human nAChR function with potencies that vary across tachykinins and nAChR subtypes. They also indicate that tachykinin actions at nAChR could further contribute to complex cross-talk between nicotinic cholinergic and tachykinin signals in regulation of nervous system activity.
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PMID:Interactions between tachykinins and diverse, human nicotinic acetylcholine receptor subtypes. 892 87

N-(4-Hydroxyphenyl)retinamide (4-HPR, Fenretinide) is a retinoid derivative with antineoplastic activity in various tumor types including prostate carcinoma. The mechanism of action of 4-HPR toxicity is unknown. 4-HPR induces apoptosis in leukemia- and lymphoma-derived cells, neuroblastoma, and small cell lung cancers. The present study was designed to investigate: (a) the mechanism of 4-HPR cytotoxicity in prostate cancer cells; and (b) correlate increased expression of transforming growth factor beta 1 (TGF beta 1) with induction of apoptosis. 4-HPR exposure to PC-3 cells in vitro was associated with apoptosis as evidenced by increased incidence of hypodiploid nuclei in propidium iodide fluorescence histograms and DNA fragmentation. An increase in the percentage of nuclei in the G1 phase of the cell cycle preceded induction of apoptosis. TGF beta 1-increased expression was noted in mRNA levels and in secretion of active TGF beta 1 into culture media. TGF beta 1 and TGF-beta receptor type II detected immunohistochemically were increased in 4-HPR-treated PC-3 cells. Furthermore, 4-HPR-induced cytotoxicity in PC-3 cells was abrogated by the addition of anti-TGF beta 1 antibody. In BT-20 cells, a 4-HPR-resistant breast carcinoma cell line, apoptosis was not observed after exposure to 4-HPR nor was TGF beta 1 expression enhanced in stained cells or in conditioned media. It is concluded that 4-HPR induces the expression of TGF beta 1 in association with the induction of apoptosis.
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PMID:Fenretinide: induction of apoptosis and endogenous transforming growth factor beta in PC-3 prostate cancer cells. 899 39

Both ice-like protease and calpain have been shown to be involved in apoptosis in non-neuronal cells. Cultured rat cerebellar granule neurons undergo apoptosis when exposed to low potassium-containing medium. Calpain inhibitors 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and N-acetyl-Leu-Leu-Met-CHO (calpain inhibitor II) as well as interleukin-beta 1 converting enzyme (ICE)-like protease inhibitor Z-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB) protect against such apoptotic death. They also reduce DNA laddering and the number of apoptotic nuclei. Staurosporine treatment also evokes apoptosis in human neuroblastoma SH-SY5Y. While Z-D-DCB is again anti-apoptotic, calpain inhibitors only provide modest effects in this model. Our results suggest that ICE-like protease plays a critical role in neuronal apoptosis whereas the contributions of calpain are more cell-type dependent.
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PMID:Effects of ICE-like protease and calpain inhibitors on neuronal apoptosis. 905 90


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