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)

Deletion of the short arm of human chromosome 1 is the most common cytogenetic abnormality observed in neuroblastoma. To characterize the region of consistent deletion, we performed loss of heterozygosity (LOH) studies on 122 neuroblastoma tumor samples with 30 distal chromosome 1p polymorphisms. LOH was detected in 32 of the 122 tumors (26%). A single region of LOH, marked distally by D1Z2 and proximally by D1S228, was detected in all tumors demonstrating loss. Also, cells from a patient with a constitutional deletion of 1p36, and from a neuroblastoma cell line with a small 1p36 deletion, were analyzed by fluorescence in situ hybridization. Cells from both sources had interstitial deletions of 1p36.2-36.3 which overlapped the consensus region of LOH defined by the tumors. Interstitial deletion in the constitutional case was confirmed by allelic loss studies using the panel of polymorphic markers. Four proposed candidate genes--DAN, ID3 (heir-1), CDC2L1 (p58), and TNFR2--were shown to lie outside of the consensus region of allelic loss, as defined by the above deletions. These results more precisely define the location of a neuroblastoma suppressor gene within 1p36.2-36.3, eliminating 33 centimorgans of proximal 1p36 from consideration. Furthermore, a consensus region of loss, which excludes the four leading candidate genes, was found in all tumors with 1p36 LOH.
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PMID:A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3. 777 41

The expression of DAN gene (previously designated as N03 gene) is significantly reduced in a variety of transformed rat fibroblasts, including v-src- (SR-3Y1), SV40- and v-mos-transformed 3Y1 cells, compared with that in parental 3Y1 cells. Recently, DAN gene has been shown to possess a tumor suppressive activity when it is overexpressed in SR-3Y1 cells (Ozaki & Sakiyama, 1994). To assess the involvement of DAN gene with human neoplasms, we have isolated human DAN counterpart from a normal lung cDNA library by using rat DAN cDNA as a probe, and determined its chromosomal location. Human DAN gene mapped to chromosome 1p36.11-p36.13, which is well known to show highly significant linkage with the genesis and/or progression of human neuroblastoma. Southern blot analysis on tumor DNA from 26 patients with neuroblastoma has detected three patients showing genomic rearrangement or deletion within or closely linked to the DAN gene locus. Collectively, we propose that human DAN gene is a possible candidate for a tumor suppressor gene of human neuroblastoma.
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PMID:Identification of human DAN gene, mapping to the putative neuroblastoma tumor suppressor locus. 808 83

DAN gene has been isolated by means of differential screening method between rat fibroblast 3Y1 and Rous sarcoma virus-transformed 3Y1 (SR-Y1) cells. DAN expression was suppressed in some of the transformed cells and its re-expression reverted the various transformed phenotypes such as colony formation in soft agar and tumor formation in mice. When DAN was overexpressed in 3Y1 cells, these cell showed the retardation of the entry into the S phase. DAN cDNA encodes a 27-kD protein which consists of 178 amino acids. The deduced amino acid sequence has no homology with known proteins. The amino terminal of DAN is highly hydrophobic and DAN is indeed secreted into the culture medium. This secreted DAN, when added to the culture of SR-3Y1 cells, suppressed DNA synthesis. Human DAN is mapped to 1p36.11-p36.13, a region known to have highly significant linkage with the genesis and/or progression of human neuroblastoma. Aberrant bands on Southern blot were detected in some of the neuroblastoma cases. Rat and human genomic DANs were isolated. CAT and the electrophoretic mobility shift assays revealed the presence of possible positive and negative regulatory elements at -57 approximately +118 and -1,232 approximately -987 of rat genome, respectively.
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PMID:[DAN gene]. 930 43

DAN gene is shown to be localized at human chromosome 1p36.11-p36.13, which resides within the consensus deletion observed in neuroblastoma. In the present study, we have isolated the genomic DNA containing the entire human DAN gene and determined its nucleotide sequence. Structural analysis revealed that DAN gene is composed of four exons and spans approximately 15 kb. Its overall structure was basically the same as that of rat DAN gene. Two distinct transcription initiation sites (major and minor) were identified by the primer extension experiment. Putative TATA and CAAT-like elements are present 38 and 366 bp upstream from the major transcription start site, respectively, however, no apparent TATA-like sequence was found in the upstream region of the minor transcription start site. The 400-bp region immediately upstream from the major transcription initiation site was strongly GC-rich (79% GC). Genomic Southern experiments demonstrated that the allelic loss of DAN gene might occur in neuroblastoma. Interestingly, there exist two dinucleotide repeats, (CA)7 and (CA)8, in the first intron of DAN gene, raising the possibility to distinguish two alleles of DAN gene in some of the cancer cells.
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PMID:The genomic analysis of human DAN gene. 932 5

Retinoic acid (RA) plays a major role in neuronal cell differentiation. Neuroblastoma cells differentiate in vitro by extending neurites and forming ganglion-like aggregates in response to RA. In the present study, we have examined a biological role(s) of DAN in the regulation of RA-mediated cellular differentiation in neuroblastoma cells. RTBM1 and SH-SY5Y cells undergo marked morphological changes associated with a remarkable induction of DAN gene expression when exposed to RA. By transfecting an expression vector harboring a rat DAN cDNA into SH-SY5Y cells, we have obtained two independent transfectants which express a large amount of DAN. The forced expression of DAN gene enhanced the neurite extension in the presence of RA, suggesting that DAN gene product might contain some regulatory role(s) in the RA-induced cellular differentiation in neuroblastoma cells.
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PMID:Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines. 950 Sep 77

Cellular, cytogenetic, and molecular evidence indicates that chromosome band 1p36 is often deleted in neuroblastoma cell lines and tumours, suggesting the presence of one or more tumour suppressor genes in this region. We used a multifaceted approach to analyse the commonly deleted region, 28 distal 1p-specific polymorphic loci were used to detect loss of heterozygosity (LOH) in a panel of primary neuroblastoma tumours. Thirty-two of 122 tumours (26%) demonstrated LOH at three or more loci. In addition, a patient with a constitutional deletion of 1p36.2-.3 and two neuroblastoma cell lines with 1p36 abnormalities were characterised by FISH. When combined with the LOH data, a single consensus region of deletion was defined proximally by PLOD and distally by D1S80, a region spanning approximately five megabases. Several proposed candidate tumour suppressor genes, including ID3, CDC2L1, DAN, PAX7, E2F2, TNFR2 and TCEB3, map outside of this region; however, the transcription factor HKR3 cannot be excluded. LOH for 1p is correlated with adverse clinical and biological features and a poor prognosis, but 1p LOH is not an independent predictor of overall survival. To identify additional candidate genes, an integrated physical map of 1p35-36 is being constructed. The current map includes 445 polymerase chain reaction (PCR)-formatted markers and 608 YACs. This map will help identify region-specific transcripts by direct selection and sequencing.
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PMID:Molecular analysis of the region of distal 1p commonly deleted in neuroblastoma. 951 32

Our previous studies have shown that the DAN gene product possesses an ability to revert phenotypes of transformed rat fibroblasts and represents a candidate tumour suppressor gene for neuroblastoma. In the present study, characterisation of DAN was carried out using rat fibroblast 3Y1 cells and their DAN-overexpressor counterparts (S-9). The N-terminal region of DAN (amino acids 1-24) was highly hydrophobic and DAN protein was found to be secreted into the culture medium. When DAN was treated with PNGase F, a enzyme that cleaves most N-linked carbohydrate residues, the mobility of both cytoplasmic and secreted DAN was increased in SDS-polyacrylamide gel electrophoresis, suggesting DAN is N-glycosylated, irrespective of its localisation. When partially purified, DAN was able, when added to the culture, to suppress DNA synthesis of Rous sarcoma virus-transformed 3Y1 cells, which lack the expression of DAN.
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PMID:A product of DAN, a novel candidate tumour suppressor gene, is secreted into culture medium and suppresses DNA synthesis. 951 39

Gene trapping in embryonic stem (ES) cells was used to identify a novel gene involved in mouse development. In order to screen trapped ES cell lines for the presence of developmentally regulated genes, an in vitro differentiation test was used. One of the G418 resistant cell lines, in conjunction with the lacZ reporter gene, showed differential expression patterns under differentiated and undifferentiated conditions. The gene trap insertion in this cell line was germ-line transmitted and X-gal staining was used to assess the expression pattern of lacZ in embryos heterozygous for the trapped allele. The reporter gene's expression was detected in commissural neurons in the developing spinal cord, suggesting functions for the trapped gene in mouse neural development. Structural analysis of the cDNA revealed that this trapped gene, named PRDC (protein related to DAN and cerberus), is a novel gene that encodes a putative secretory protein consisting of 168 amino acid residues. PRDC gene product shows limited similarities to the products of DAN (differential screening-selected gene aberrative in neuroblastoma) and cerberus. (DAN is a possible tumor-suppressor for neuroblastoma in human. Cerberus can induce an ectopic head in Xenopus embryos when ectopically expressed.) These three gene products may form a novel family of signaling molecules.
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PMID:Sequence and expression of a novel mouse gene PRDC (protein related to DAN and cerberus) identified by a gene trap approach. 963 62

DAN gene was first isolated by differential screening between rat 3Y1 and v-src-transformed 3Y1 cells and showed a tumor-suppressive activity toward v-src-transformed 3Y1 cells. When DAN-transfected neuroblastoma cells were treated with a tumor promoter phorbol ester, TPA, neurite-like processes appeared within 2 h whereas no apparent change was observed in the parent and vector-transfected cells up to 8 h. This suggests some difference in TPA-receptor, protein kinase C (PKC), between DAN-transfectants and the control cells. DAN-transfected SH-SY5Y cells showed complete loss in PKCalpha and a large decrease in PKCgamma. Similar down-regulation in PKCalpha and PKCgamma was also observed in DAN-transfected Ha-ras-transformed NIH 3T3 cells. The decreased level of PKCalpha was partially recovered after treatment with a calpain inhibitor, ZLLH. A 150-kDa proteolytic product of a calpain-specific substrate, non-erythroid alpha-spectrin, was detectable in DAN-transfected SH-SY5Y cells but not in the parent or vector-transfected control cells. This suggests that DAN-transfected cells contain activated calpain which may cause down-regulation of PKC and hence induce the altered TPA response.
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PMID:Down-regulation of protein kinase C alpha and gamma and enhanced TPA-induced neurite formation in DAN-transfected neuroblastoma cells. 986 17

Distal alterations of the short arm of chromosome 1 are among the most frequent cytogenetic abnormalities in human breast carcinoma. We studied 96 primary human breast carcinomas for allelic imbalance using a panel of 31 polymorphic microsatellite, restriction fragment length polymorphism, and variable number of tandem repeat markers located mainly in the 1p32-pter region. Allelic imbalance at one or more loci was observed on the short arm of chromosome 1 in 56 (58.3%) of the 96 tumors. The 56 1p-altered tumor DNAs showed loss of heterozygosity (LOH), 12 (21.4%) at all informative loci tested and 44 (78.6%) at some loci. The LOH pattern of these 44 partially deleted tumors identified two distinct consensus regions of deletion on 1p32-pter (1p36.3 and 1p32). These regions match those described by other investigators but are considerably smaller. The 1p32 band is located within one of the two 1p regions of LOH in neuroblastoma, suggesting the involvement of the same unidentified tumor suppressor gene in both human breast cancer and neuroblastoma. The candidate tumor suppressor genes TNFR2, RIZ, DAN, RAP1GA1, FGR, MDGI, EXTL, and hRAD54 were excluded from the two consensus regions of deletion identified at 1p32-pter. Analysis of six polymorphic markers chosen to map within the other deleted regions described in breast tumors confirmed that two additional breast tumor suppressor genes are located in the proximal part (1p22 and 1p13) of chromosome arm 1p. Taken together, these results suggest that several unknown suppressor genes on 1p might be involved in the development of breast cancer. The refinement of the regions of LOH to within a few cM, and the recent publication of transcript maps of the human genome, mean that candidate genes and expressed sequence tags mapping to these deleted regions can now be investigated.
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PMID:Deletion mapping of chromosomal region 1p32-pter in primary breast cancer. 1045 6


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