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)

Intracisternal A-particle (IAP)-specific sequences were 5- to 10-fold enriched in polyadenylated RNA from BALB/cJ thymus as compared with RNAs from liver, spleen, and kidney. The major transcripts of 7.2 and 5.4 kilobases were the same size as those found in an IAP-rich neuroblastoma cell line. The absolute levels and proportions of these transcripts varied in thymuses from mice of different inbred strains. With antiserum prepared against p73, the main IAP structural protein, several size classes of IAP-related proteins were immunoprecipitated from extracts of thymus cells incubated with [35S]methionine; these included p73 itself and a group of polypeptides in the size range of 114 to 120 kilodaltons (p114-p120). The inbred strains showed marked characteristic differences in the electrophoretic patterns of their IAP-related proteins. Earlier studies showed that the 7.2-kilobase RNA from neuroblastoma IAPs coded for p73 in a cell-free translation system. Correlations between the RNA and protein patterns in thymuses of the different inbred strains indicated that 5.4-kilobase RNA gives rise to the p114-p120 polypeptides. Metabolically labeled p120 was found to include methionine-containing tryptic peptides of p73 plus additional peptides consistent with its larger size. In vivo labeling kinetics showed that the p114-p120 polypeptides were not major precursors of p73 in intact neuroblastoma cells. This study shows that IAP gene expression in mouse thymus is genetically determined and that a novel class of IAP-related polypeptides can be expressed independently of the major particle structural protein.
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PMID:Intracisternal A-particle gene expression in normal mouse thymus tissue: gene products and strain-related variability. 285 19

We describe a gene encoding p73, a protein that shares considerable homology with the tumor suppressor p53. p73 maps to 1p36, a region frequently deleted in neuroblastoma and other tumors and thought to contain multiple tumor suppressor genes. Our analysis of neuroblastoma cell lines with 1p and p73 loss of heterozygosity failed to detect coding sequence mutations in remaining p73 alleles. However, the demonstration that p73 is monoallelically expressed supports the notion that it is a candidate gene in neuroblastoma. p73 also has the potential to activate p53 target genes and to interact with p53. We propose that the disregulation of p73 contributes to tumorigenesis and that p53-related proteins operate in a network of developmental and cell cycle controls.
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PMID:Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. 928 59

Genetic alteration of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human colorectal carcinoma (CRC). Recently, p73, a novel family member of p53, has been identified and found, like p53, to activate p21Waf1/Cip1 and to induce apoptosis. The p73 gene was mapped at chromosome 1p36.3 which is a region frequently deleted in CRCs and other cancers including neuroblastoma. To assess whether or not p73 is a tumor suppressor gene of CRC, we performed mutational analysis of p73 in 82 colorectal tumor tissues paired with constitutional DNA. Using a microsatellite marker for p73, the loss of heterozygosity (LOH) study was performed and allelic loss of p73 was found in 17% of the CRCs. RT-PCR single strand conformation polymorphism analysis showed no mutation except three polymorphisms in the p73 coding region. In addition, p73 was expressed at higher levels in the CRC tissues than in the normal mucosa or neuroblastoma tissues, though the transcripts were detectable only by the RT-PCR method. Our results suggest that, in CRCs, p73 may not play a role as a tumor suppressor, at least not in a classic Knudson manner.
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PMID:Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas. 966 27

The p53 protein, which regulates the rate of cell division and death, is the most frequently mutated tumor suppressor to be identified so far in human cancers. Recently, a gene with significant homology to p53, termed p73, has been identified in a chromosomal region that is implicated in the molecular pathogenesis of neuroblastoma. We have cloned a second human p53-related gene, termed p73L, which shows strong amino-acid similarity to p73. The p73L gene is mapped to human chromosome 3q27-28 using in situ hybridization technique. p73L encodes a protein of 586 amino acids and its putative DNA binding domain (DBD) has high identities to those of p53 (60.6%) and to p73 (87.8%). Northern blot analysis, which demonstrated that the expression profiles of p73L and p73 mRNAs are distinct in some tissues, implies that p73 and p73L may have separate, distinct roles in different tissues.
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PMID:A second p53-related protein, p73L, with high homology to p73. 970 73

p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whether p73 is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron-exon boundary sequences of the p73 gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in the p73 gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear that p73 is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.
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PMID:Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. 972 Dec 6

A novel gene, termed p73, encodes a protein with a significant homology to p53 and has been mapped at chromosome 1p36.3, which is a locus of multiple suppressor genes for tumors including neuroblastoma and other cancers. Since the 1p36 locus is reported to be deleted and p53 is frequently mutated in esophageal carcinomas, we examined loss of heterozygosity (LOH) and mutation of the p73 gene in 48 untreated esophageal tumors, as well as mRNA expression in 8 tumors. We screened the P1 genomic library to obtain a P1 clone containing the p73 gene and found a polymorphic short tandem CT repeat site at intron 9. Intragenic sequences for 14 PCR primer sets and a primer pair flanking the repeat were also determined for the analysis of PCR single-strand conformation polymorphism (SSCP) and LOH studies, respectively. Expression of p73 mRNA was detectable but at low levels in all 8 tumor tissues by reverse transcriptase PCR. We did not find any type of mutation other than polymorphisms in the 48 esophageal carcinomas, though aberration of the p53 gene on the PCR-SSCP gels was observed in 15 of 38 (39%) tumors of the same set. In addition, LOH for p73 was found in only 2 of 25 (8%) tumors. These results suggest that, at least in esophageal carcinomas, allelic loss or mutation of p73 may not be a main genetic event for the tumorigenesis as it is with p53.
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PMID:p73, a gene related to p53, is not mutated in esophageal carcinomas. 979 31

p73 has been recently identified as a new structural and functional homologue of the transcription factor p53. It is expressed in either a full-length form, alpha, or a shorter beta mRNA variant, with exon 13 spliced out. Here we report the identification and functional characterization of two new p73 splicing variants, gamma (splicing out exon 11) and delta (splicing out exons 11, 12, and 13). Both gamma and delta p73 variants are expressed in human peripheral blood lymphocytes, primary keratinocytes, and different tumor cell lines, including neuroblastoma, glioblastoma, melanoma, hepatoma, and leukemia. The expression pattern of the four p73 splicing variants differs in both primary cells of different lineage and established cell lines even within the same type of tumor. A two-hybrid assay was used to characterize the homodimeric and heterodimeric interactions between the p73 variants, and showed that neither p73gamma nor p73delta interact with p53, whereas p73gamma showed strong interactions with all p73 isoforms, and p73delta binds efficiently p73alpha and p73gamma but only weakly p73beta. At the functional level, p73gamma is significantly less efficient in activating transcription of the p21(Waf1/Cip1) promoter than p53 or p73beta, whereas the effect of p73delta is intermediate and comparable to that of p73alpha. The ability of the different p73 variants to affect cell growth in p53 null osteosarcoma SAOS-2 cells correlates with their transcriptional activity on the p21(Waf1/Cip1) promoter: p73beta is the most efficient in inhibiting colony formation, whereas p73gamma is almost ineffective. Our results suggest that p73 isoforms may be differentially regulated, with four different isoforms capable of interacting among themselves and with p53. The relative expression level of each splice variant may modulate p73 transcriptional and growth suppression activities by affecting heterodimer formation.
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PMID:Two new p73 splice variants, gamma and delta, with different transcriptional activity. 980 88

The novel p73 gene is a structural and, in overexpression systems, functional p53 homologue. p73 resides on chromosome 1p36.33 within a commonly deleted region in neuroblastoma (NB) and other human tumors. To evaluate p73's candidacy for a NB suppressor, we analyzed 28 primary NB tumors, 14 NB cell lines, and 5 non-NB malignant pediatric tumors. We determined the level of p73 expression and its allelic origin and searched for mutations. Fifty-one different types of normal tissues all showed very low p73 expression. Although most NB tumors expressed p73 within the normal tissue range, wild-type p73 expression levels varied widely in NB and non-NB tumors and NB cell lines with increases up to 90-fold compared with normal tissues. Importantly, the p73 gene was biallelically expressed in five of six NB tumors and three of three normal tissues. Mutation analysis of the entire open reading frame of the gene in 16 tumors (including all 6 highly expressing tumors) revealed four polymorphic sites, but no mutations. Collectively, our data argue that p73 is unlikely to be a suppressor gene inactivated during neuroblastoma development.
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PMID:Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines. 983 Dec 42

p73, a novel p53 family member, is a recently identified candidate neuroblastoma (NBL) suppressor gene mapped at chromosome 1p36.33 and was found to inhibit growth and induce apoptosis in cell lines. To test the hypothesis that p73 is a NBL suppressor gene, we analysed the p73 gene in primary human NBLs. Loss of heterozygosity (LOH) for p73 was observed in 19% (28/151) of informative cases which included 92 mass-screening (MS) tumors. The high frequency of p73 LOH was significantly associated with sporadic NBLs (9% vs 34%, P<0.001), N-myc amplification (10% vs 71%, P<0.001), and advanced stage (14% vs 28%, P<0.05). Both p73alpha and p73beta transcripts were detectable in only 46 of 134 (34%) NBLs at low levels by RT-PCR methods, while they were easily detectable in most breast cancers and colorectal cancers under the same conditions. They found no correlation between p73 LOH and its expression levels (P>0.1). We found two mutations out of 140 NBLs, one somatic and one germline, which result in amino acid substitutions in the C-terminal region of p73 which may affect transactivation functions, though, in the same tumor samples, no mutation of the p53 gene was observed as reported previously. These results suggest that allelic loss of the p73 gene may be a later event in NBL tumorigenesis. However, p73 is infrequently mutated in primary NBLs and may hardly function as a tumor suppressor in a classic Knudson's manner.
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PMID:p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent. 1002 82

The p73 gene encodes a protein that shares structural and functional homologies with the p53 tumor suppressor protein. The p73 gene is monoallelically expressed in normal tissue, maps to chromosome 1p36 and is deleted in human neuroblastoma cell lines. Alternative splicing of exon 13 in p73 transcripts generates two isoforms, p73alpha and p73beta, that differ in their carboxy-terminus and in their ability to form homotypic interactions. In this study, we investigated, in 129 human central nervous system tumors of various histological types, the levels of p73 transcripts and the splicing characteristics of p73 mRNA. Whereas p73 mRNA content was consistently low in most tumoral types, especially in meningiomas, some glioblastomas, medulloblastomas and metastases exhibited elevated p73 mRNA content. However, ependymomas expressed consistently high amounts of p73 mRNA, significantly different from the other tumoral types. Whereas the short (p73beta) isoform accounted for 20-25% of the total p73 mRNA in most of the tumors, these splicing characteristics were altered in ependymomas (only 9% of p73beta) and in neurinomas (up to 53% of p73beta). These observations suggest tissular or tumoral differences in the control of p73 gene transcription and alternative splicing, and raise the problem of the role of p73 isoforms in the control of tumor growth, particularly in ependymomas.
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PMID:p73 gene transcripts in human brain tumors: overexpression and altered splicing in ependymomas. 1021 63


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