UMLS:C0027819 - FACTA Search

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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

We have previously demonstrated (A. H. Batchelor and P. O'Hare, J. Virol. 64:3269-3279, 1990) the selective activity in human neuroblastoma cells (IMR-32) of a promoter located upstream of the latency-associated transcript of herpes simplex virus type 1. In this work, we provide evidence for the basis of the selective activity of this latency-associated promoter (LAP). Recombinant constructs containing sequences up to -143 (relative to the LAP cap site) linked to the chloramphenicol acetyltransferase gene retain strong activity in HeLa cells but exhibit extremely weak activity in IMR-32 cells. Sequences mapping within the 108 bp upstream of -143 to position -251 enhance LAP activity by over 15-fold, restoring optimal levels of expression in IMR-32 cells, but have little or no effect (1.5-fold) in HeLa cells. This cell-type-specific enhancement of promoter activity took place in two major steps, with sequences between -143 and -158 conferring a four- to fivefold effect and sequences between -177 and -251 conferring a further threefold effect. Furthermore, sequences mapping from -40 to -258 could transfer the ability to be expressed in neuroblastoma cells to the normally inactive immediate-early 110K promoter (IE110K), increasing levels of expression by 35-fold. By comparison, this region had a relatively minor effect (twofold) on the activity of the IE110K promoter in HeLa cells, even though this promoter is open to activation by other mechanisms. However, neither of the overlapping subregions from -40 to -143 or -138 to -258 could confer efficient IMR-32 cell expression on the IE110K promoter, and we present alternative models for multiple element requirements or the requirement for a critical site around -140 which is not retained in either subfragment. We provide consistent evidence for a site around -140 and demonstrate the presence selectively in IMR-32 cells of a DNA-binding factor which binds a probe spanning this region. We propose that this element and the cognate factor (IC-1) may be involved in the selective activity of the LAP in neuroblastoma cells.
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PMID:Localization of cis-acting sequence requirements in the promoter of the latency-associated transcript of herpes simplex virus type 1 required for cell-type-specific activity. 131 69

The various members of the myc gene family, including c-myc and N-myc, are supposed to play a role in the regulation of cell cycle and proliferation. Whereas c-myc is expressed nearly ubiquitously, the N-myc gene product is found mainly in actively proliferating neural tissues such as early development tissues or in retinoblastomas and neuroblastomas. In this report, the upstream region of mouse N-myc gene was ligated to pSVPCAT, which carries the simian virus 40 (SV40) promoter and bacterial chloramphenicol acetyltransferase (CAT) gene, and transcriptional activities were examined by CAT and S1 protection assays after transfection of the DNAs into human cervical carcinoma HeLa or neuroblastoma IMR32 cells. Several regulatory regions were identified: two promoting regions (-980 to -860 and -279 to +108) and an inhibiting one (-860 to -797). The region spanning positions -980 to -860 increased CAT expression independently of orientation and distance to the SV40 promoter, indicating that the element is a typical enhancer. Moreover, the expression levels from this enhancer were higher in IMR32 cells than in HeLa cells, indicating that action has, if not cell-type specificity, cell-type preference. These findings may provide useful bases for the understanding of the cell-type specific regulation of N-myc expression.
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PMID:The upstream region of the mouse N-myc gene: identification of an enhancer element that functions preferentially in neuroblastoma IMR32 cells. 132 47

The 5'-flanking region of the calcineurin A alpha gene was isolated from a rat genomic library. It lacked TATA and CAAT boxes but contained G+C-rich regions, and was demonstrated to function as a strong promoter in neuronal cell lines (NG108-15 mouse neuroblastoma x rat glioma hybrid cells or N1E115 mouse neuroblastoma cells), but not in nonneuronal cell lines (C6 rat glioma or L-M mouse fibroblastoid cells) in a transient chloramphenicol acetyltransferase expression assay. Deletion analysis of the 5'-flanking region revealed that the core promoter region, as well as the sequence critical for cell-type-specific-promoter function, reside within the fragment -107 to +157 with respect to the major transcription initiation site.
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PMID:Molecular cloning and characterization of the promoter region of the calcineurin A alpha gene. 133 33

It is well documented that cold stress induces a rapid trans-synaptically mediated increase in the relative abundance of rat adrenomedullary tyrosine hydroxylase (TH) mRNA. To investigate the transcriptional mechanisms regulating the cold stress response, we have employed a gel mobility shift assay, using DNA fragments prepared from the proximal 5' flanking region of the bovine TH gene as a heterologous molecular probe. In pilot studies, this region of the bovine TH promoter (nucleotides -246 to +21) was fused to the bacterial reporter gene, chloramphenicol acetyltransferase, and the chimeric construct transfected into human neuroblastoma SK-N-BE(2)-C, hepatoma HepG2, and rat pheochromocytoma PC-12 cells. Results of this analysis indicate that the proximal 5' flanking region of the bovine TH gene contains sufficient information to drive transient reporter gene expression in both human and rat catecholaminergic clonal cell lines. The findings derived from the gel mobility shift studies demonstrate that cold exposure causes rapid and selective alterations in the binding of adrenomedullary nuclear proteins to the proximal 5' flanking region of the TH gene. The most striking cold stress-induced alteration in DNA/nucleoprotein binding occurs in a region of the TH promoter (nucleotides -246 to -189) which contains an element bearing marked sequence similarity to an AP1 binding site and is highly conserved among animal species. This alteration occurs within 1 hr of cold exposure and persists for up to 48 hr after the onset of stress. The results of adrenal denervation experiments indicate that the cold-induced change in DNA/nucleoprotein binding is neurally mediated, requiring intact sympathetic innervation of the gland.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cold-induced alterations in the binding of adrenomedullary nuclear proteins to the promoter region of the tyrosine hydroxylase gene. 136 May 41

The regulation of human corticotropin-releasing hormone (hCRH) gene promoter activity by inducers of cAMP was investigated by transient transfection with a construct containing the hCRH gene promoter fused to the chloramphenicol acetyltransferase gene. Expression of hCRH-chloramphenicol acetyltransferase was strongly enhanced by forskolin in the neuroblastoma SK-N-MC and choriocarcinoma JAR cell lines. Overexpression of the catalytic subunit of protein kinase A dispensed the need for forskolin, and cotransfection of cAMP-responsive element-binding protein cDNAs enhanced forskolin-dependent expression of the hCRH promoter. Progressive 5'-end deletions of the hCRH promoter delineated a cAMP- responsive region between -226 and -164 base pairs. This fragment contained the sequence TGACGTCA at -221 base pairs, consistent with the consensus motif for a CRE. A homologous oligonucleotide responded to cAMP when cloned in either orientation in front of the thymidine kinase promoter. However, the level of constitutive and inductive cAMP expression was dependent on the cell line and on intrinsic properties of the promoter. Mutation of the wild type CRH-CRE sequence into an AP-1 site (TGAGTCA) completely abolished stimulation by cAMP. In contrast, coexpression of the catalytic subunit of protein kinase A dispensed the need for stimulation with forskolin, which showed that the CRH-CRE oligonucleotide served as a functional equivalent of the native CRE element.
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PMID:Identification and characterization of a 3',5'-cyclic adenosine monophosphate-responsive element in the human corticotropin-releasing hormone gene promoter. 148 Jan 79

We cloned, sequenced and characterized a promoter region of the mouse homologue of the Alzheimer's disease amyloid precursor protein (APP)-encoding gene. The promoter region is highly homologous to that of the human APP (hAPP) gene. It has a high G+C content, lacks typical 'TATA' and 'CAAT' boxes, and contains possible binding sites for AP-1, heat-shock factor, Sp1 and AP-4. The promoter region was fused with the cat reporter gene, and the fusion genes were transfected to both the NB41A3 (mouse neuroblastoma) and L-cell lines. The promoter activity was monitored by chloramphenicol acetyltransferase (CAT) activity in a transient expression assay. The promoter was equally active in both cell lines. The deletion analysis revealed that there existed a negative regulatory element(s) between -153 and -100 bp and a positive element(s) between -100 and -37 bp. The negative element was shown to suppress the transcriptional activity of heterologous simian virus 40 promoter. DNase I footprinting experiments revealed that three nuclear protein-binding sites existed in the regulatory region, one in the negative and two in the positive regulatory regions. Gel retardation assay showed that Sp1 was one of the factors binding to the positive regulatory region. A nuclear factor binding to the negative regulatory region seemed to be missing in brain.
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PMID:Positive and negative regulatory elements for the expression of the Alzheimer's disease amyloid precursor-encoding gene in mouse. 155 68

To study how the expression of the D1A dopamine receptor gene is regulated, a human genomic clone was isolated by using a rat cDNA as probe. A 2.3-kilobase genomic fragment spanning -2571 through -236 relative to the adenosine of the first methionine codon was sequenced. The gene has an intron of 116 base pairs in the 5' noncoding region, nucleotides -599 through -484 as determined by S1 mapping and reverse transcription-PCR. It has multiple transcription initiation sites located between -1061 and -1040. The promoter region lacks a TATA box and a CAAT box, is rich in G+C content, and has multiple putative binding sites for transcription factor Sp1. Thus, the promoter region of the human D1A gene has features of "housekeeping" genes. However, it also has consensus sequences for AP1 and AP2 binding sites and a putative cAMP response element. The ability of four deletion mutants of the 2.3-kilobase fragment to modulate transcription of the heterologous chloramphenicol acetyltransferase gene in the promoterless plasmid pCAT-Basic was determined. All mutants demonstrated substantial transcriptional activity in the murine neuroblastoma cell line NS20Y, which expresses the D1A gene endogenously. Transient expression assays suggested the presence of a positive modulator between nucleotides -1340 and -1102, and a negative modulator between -1730 and -1341. The four genomic fragments had no or very low transcriptional activity in NB41A3, C6, and Hep G2 cells, which are not known to express this gene. Thus, the human D1A gene belongs to the category of tissue-specific, regulated genes that have housekeeping-type promoters.
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PMID:Characterization of the 5' flanking region of the human D1A dopamine receptor gene. 155 11

The induction of human immunodeficiency virus type 1 (HIV-1) gene expression by cytokines was investigated in cells of central nervous system origin. These were human neuroblastoma, glioblastoma, and astrocytoma cell lines, a murine oligodendroglioma and primary murine astrocyte cultures. The cytokines used were tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, and interferons alpha and gamma (IFN alpha, gamma). Transient transfection of cells with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of the HIV-1 long terminal repeat (LTR) showed significant augmentation following treatment by particular cytokines. TNF alpha was found to augment HIV LTR-directed CAT activity in all cell types. IL-1 beta also activated the HIV LTR reporter gene in glioblastoma, astrocytoma, and astrocyte cells. IL-6 enhanced HIV gene expression in one example only, the primary astrocyte cultures. The interferons generally suppressed expression from the LTR except IFN gamma which produced a twofold rise in the murine glial cells and IFN alpha augmenting expression in one neuroblastoma cell line. No synergy was observed between pairs of activating cytokines tested. The HIV tat gene product was found to be functional in all cells, cotransfection of a tat expression vector transactivating expression from the LTR, with varying degrees of efficiency. In some cell lines the combination of an activating cytokine and tat resulted in an enhancement above that obtained by cotransfection of tat alone. In others, the level of CAT activity did not significantly change. Analysis of nuclear extracts from cytokine-treated cells further implicated the involvement of NFKB in the induction of HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. 159 55

Retinoids are known to have profound effects on cellular differentiation and embryo pattern formation. In the adult organism, retinoid acid (RA) receptors are present in a large variety of tissues, including brain. However, little is known of the precise roles of RA at these different sites. In the present study we have identified a novel potential target of RA action by identifying an RA response element (RARE) in the human oxytocin (OT) gene promoter. We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells. RA elicited a marked stimulation of the transcriptional activity of the OT promoter in cells cotransfected with either the human RA receptor alpha, beta, or gamma. In cells cotransfected with the RA receptor alpha, the ED50 of this response was 5 x 10(-10) M. The RA response could also be conferred to a heterologous promoter independent of orientation. 5'-Deletions as well as site-directed mutations demonstrated that four TGACC motifs, located at -162, -156, -103, and -83 in the OT promoter, are necessary for optimal RA induction. Mutation or deletion of any of these elements reduces significantly the RA response. Interestingly, the first two TGACC motifs overlap with the estrogen response element that we have previously characterized in this gene. Furthermore, the TGACC motif located at -83 overlaps with the CCAAT box. We further demonstrate that in neuroblastoma cells transfected with an RAR alpha expression vector expression of the endogenous OT gene is stimulated greater than 4-fold in response to RA. Our studies constitute the first report of a RARE in a neuropeptide gene and define a mechanism by which OT gene expression can be modulated by retinoic acid.
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PMID:Identification of a retinoic acid response element in the human oxytocin promoter. 165 67

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