Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently reported that the statistical analysis of the frequency distribution of short oligonucleotides within mammalian and viral genomes allows the production of sets of DNA sequences enriched in signals for transcription factors. Such statistical approaches could facilitate the identification of new promoter regions playing a role in the transcriptional regulation of gene expression. In the case of mammalian oligonucleotides, we found that the published set of frequent decamers enriched in transcriptional motifs is not suitable for studies on genes of Homo sapiens and evolutionarily related genomes, because it contains decameric sequences belonging to genomic repeats. We report here that most of the decameric sequences of DNA repeats belong to Alu repeats. Accordingly, we produced a subset of Alu-free frequent decamers. In addition, we eliminated from the subset of Alu-free frequent decamers those that are frequently present within other common human repeats, including (GT)n, (AT)n, (CA)n, (ATT)n, (CAA)n and (GTT)n. The Alu-free (repeats-free) subset of frequent mammalian decamers is enriched in signals for transcription factors and allows the identification of putative signals in genes, such as those coding for plasminogen activator, adenosine deaminase and p53, that contain a large number of Alu-like repeats interspersed within our genomic sequences. The newly generated compilation of frequent decamers described here might be used to locate genomic regions playing functional roles in the expression of genes of Homo sapiens and related primates.
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PMID:A set of Alu-free frequent decamers from mammalian genomes enriched in transcription factor signals. 782 65

In an effort to define the pathogenic relationship between ovarian neoplasms spanning the clinicopathological spectrum from benign to malignant, the incidence of Ki-ras and p53 mutations was determined in 20 ovarian cystadenomas, 20 low malignant potential (LMP) tumors of the ovary, and 23 ovarian carcinomas. Using DNA extracted from paraffin embedded tissue, polymerase chain reaction amplification, designed restriction fragment length polymorphism analysis, and DNA sequencing, 1 cystadenoma (5%), 6 LMP tumors (30%), and 1 ovarian carcinoma (4%) demonstrated an activated Ki-ras gene. All of the Ki-ras mutations identified except one were GGT to GAT transversions at codon 12. One LMP tumor demonstrated a CAA to CAC transversion at codon 61. Using polymerase chain reaction/single strand conformational polymorphism, DNA sequencing, and immunohistochemistry, 11 ovarian carcinomas (48%) demonstrated a p53 mutation. These mutations included 5 missense, 2 nonsense, and 1 frameshift mutation located within exons 6-8 and 3 mutations that were identified only by immunohistochemical staining. No p53 mutations could be identified in cystadenomas or LMP tumors. Clinically, the presence of either a Ki-ras or p53 mutation was associated with advanced stage disease. The pattern of Ki-ras and p53 mutations appears to distinguish LMP tumors from invasive carcinomas and suggests that they may be separate biological entities.
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PMID:p53 and Ki-ras gene mutations in epithelial ovarian neoplasms. 831 18

Anaplastic thyroid carcinoma (ATC) is usually associated with a poor prognosis, with most patients dying within a few months. The mechanism of its carcinogenesis is unclear, and its rapid growth and spread often prevent effective surgical therapy. Thus, chemotherapy is necessary. However, ATC is often resistant to anticancer drugs. Therefore, prediction of chemosensitivity is important in selecting appropriate treatment. In this study, after the establishment of three cell lines (K119, KOA2, and IAA) from patients with ATC, we analyzed them for abnormalities in certain oncogenes (myc, ras, ret, and c-erbB2) and the p53 tumor suppressor gene. Only one of three cell lines (KOA2) had a N-ras mutation [codon 61 CAA(Gln)-->CGA(Arg)] and a p53 gene mutation [exon 6 codon 192 Caa(Gln)-->TAG(stop)]. We also investigated their in vitro drug sensitivity and compared it with clinical chemosensitivity, retrospectively. In vitro drug sensitivity was determined using an adhesive tumor cell culture system. Only the K119 cells were sensitive to adriamycin and cisplatin in vitro. The other two were resistant to them in vitro. These results paralleled the clinical responses. We also evaluated the in vitro drug sensitivity of a poorly differentiated thyroid carcinoma cell line (SMP) and papillary thyroid carcinoma cell lines (NPA). None of the five cell lines expressed the multidrug resistance gene (mdr-1). In conclusion, we established ATC cell lines that are suitable models for characterizing the nature of multidrug resistance and carcinogenesis.
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PMID:Establishment of anaplastic thyroid carcinoma cell lines useful for analysis of chemosensitivity and carcinogenesis. 885 99

We report 8 newly established gastric-carcinoma cell lines (SNU-216, 484, 520, 601, 620, 638, 668, 719) from Korean patients. Morphologic study was carried out using light and electron microscopes. CEA, alpha FP, and CA 19-9 and TPA in supernatant and in cell lysate were measured by radioimmunoassay. p53 and c-Ki-ras gene mutations were screened and confirmed by sequencing. The cell lines, derived from tumors with moderate differentiation, grew as a diffuse monolayer, and those from tumors with poor differentiation and minimal desmoplasia grew exclusively as non-adherent. Out of the 8 gastric-cancer cell lines, 5 had detectable levels of CEA both in supernatant and in cell lysate; there was no expression or secretion of alpha FP in these cells; 4 cell lines showed high levels of CA 19-9 in cell pellets. All cell lines except SNU-484 had high concentrations of TPA both in cell lysate and in supernatants. p53 mutation was found in 6 cell lines (75%): 2 (SNU-216 and SNU-668) had mutations in exon 6, and other 3 in exon 8. The c-Ki-ras mutation was found in 2 cell lines (25%), SNU-601 and SNU-668. The former showed GGT-to-GAT transition mutation at codon 12, while the latter showed CAA-to-AAA transversion mutation at codon 61. DNA profiles using restriction endonuclease HinfI and polymorphic DNA probes ChdTC-15 and ChdTC-114 showed different unique patterns; which suggests that these cell lines are unique and not cross-contaminated. We believe that the newly characterized gastric-cancer cell lines presented in this paper will provide a useful in vitro model for studies related to human gastric cancer.
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PMID:Establishment and characterization of human gastric carcinoma cell lines. 903 53

Eighteen human congenital melanocytic naevi (CMN) from 17 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 and for sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis. In addition, all lesions were screened for deletions and point mutations in the tumour suppressor genes p53 and p16INK4a (CDKN2A) by combined multiplex PCR/SSCP analysis. Positive screening data were specified by sequencing of the corresponding PCR product. Activating point mutations in the N-ras gene (nine CAA (Gln) to AAA (Lys) transversions and one CAA (Gln) to CGA (Arg) transition at codon 61) were detected at high frequency (56%). Furthermore, three missense mutations (V92M) and two silent mutations (CGA (Arg) to CGG (Arg), codon 213, exon 6) were found in the MC1R and p53 genes, respectively. No mutations were found in p16 or CDK4. The activated N-ras oncogene, which is also found in human cutaneous melanomas, may constitute a potential risk factor for melanoma formation within CMN.
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PMID:Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi. 1046 11

Vinyl chloride is a potent hepatocarcinogen which reacts with DNA to generate etheno bases. In order to determine whether mutational patterns in target genes in vivo are characteristic of vinyl chloride and could be explained by the mutagenic properties of the etheno bases, human and rat liver tumours associated with exposure to vinyl chloride were analysed for point mutations in the ras and p53 genes. In this paper, we review these data and report our latest results on animal tumours. Two alterations were found which could be attributed to a direct effect of vinyl chloride: a GC-->AT transition which leads to a GGC-->GAC mutation at codon 13 of the Ki-ras gene in human liver angiosarcomas, and lesions at AT base pairs, mostly AT-->TA transversions, which lead to mutations in the p53 gene in human and rat angiosarcomas and to a CAA-->CTA mutation at codon 61 of the Ha-ras gene in rat hepatocellular carcinomas.
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PMID:Vinyl chloride-specific mutations in humans and animals. 1062 31

We have analyzed the expression of the CDKN1A (p21(CIP1)), CDKN1B (p27(Kip1)), TP53, RB1 and MDM2 proteins and tumor cell proliferation by immunohistochemical staining in 59 cases of metastatic melanoma. The genomic status of the CDKN2A (INK4-ARF, p16/p14(ARF)), CDKN2B (p15) and CDKN2C (p18) genes was determined by PCR-SSCP (single-strand conformation polymorphism) in 46 of these cases. These results were correlated with various clinico-pathological parameters, including the outcome of combined chemoimmunotherapy. We found positive correlations between the expression of CDKN1A and MDM2 (r = 0.5063, P = 0.001), between the expression of CDKN1B and RB1 (r = 0.5026, P = 0.001), and between RB1 expression and tumor cell proliferation (0.5564, P<0.001). Two mutations in the CDKN2A (p16) gene were detected, including a novel base change AAC-->ATC (Asn to Ile) at codon 71, that also changes the codon 85 of the alternative reading frame gene p14(ARF) from CAA to CAT (Gln to His). Homozygous deletion at exon 2 of the CDKN2A (INK4-ARF) gene was detected in six cases. In seven cases, the 540C-->G polymorphism in the 3'UTR of the CDKN2A (p16) gene was found in linkage disequilibrium with the 74C-->A polymorphism in intron 1 of the CDKN2B gene (P < 0.0001). These cases had significantly lower expression of the TP53 protein (P = 0.0032). Both 540C-->G and 580C-->T polymorphisms in the 3'UTR of the CDKN2A (p16) gene were associated with significantly shorter progression time from primary to metastatic disease (P = 0.0071). We conclude, that although none of the analyzed cell cycle regulators could be singled out as a major prognostic factor, G(1)/S checkpoint abnormalities remain one of the most significant factors in the development of malignant melanoma.
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PMID:Analysis of G(1)/S checkpoint regulators in metastatic melanoma. 1086 49

Leukemia, a form of haematological malignancy, is a multi-stage disease and a wide range of diverse genes has been speculated to correlate with its initiation and development. Ras has been speculated to be an initiating gene for haematological malignancy, but more investigation will be needed to determine the genes associated with the progression of the disease. 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat leukemia provides a good tool for research into various stages of the disease. The entire coding regions of p53 and ras genes were examined for mutations in the present study. In this experiment, we used fluorescence-labeled polymerase chain reaction single-stranded conformation polymorphism analysis (PCR-SSCP) and direct sequencing to detect mutations of both genes on rat erythroleukemia. Fifteen out of 18 (83.3%) rat leukemias were found to have N-ras codon 61 mutation, consistent with previous results. The result of direct sequencing showed a single base substitution (CAA to CTA), resulting in an amino-acid change from Gln to Leu. No mutations were found in H-ras, K-ras or codon 12 of N-ras. The incidence of p53 gene mutation was 16.6% (3/18) in rat leukemia at late-stage. In the present study, mutation of the p53 gene was detected in three DMBA-induced leukemias as follows: a single-base substitution (CAT to CGT) at codon 177 (exon 5), resulting in an amino-acid change from Arg to Leu, a CGG to CTG/CGG changed at codon 211 (exon 6) resulting in an amino-acid change from His to Arg/His, and a GGG to TGG at codon 242 (exon 6) resulting in an amino-acid change from Gly to Trp, respectively. Thus, mutations of p53 gene do not seem to respond to the carcinogenesis of the DMBA-induced leukemia, in contrast to mutation of the N-ras oncogene, and may possibly be involved in the progress of multi-stage leukemogenesis.
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PMID:Incidence of p53 and ras gene mutations in DMBA-induced rat leukemias. 1238 83

The BUB1 gene is a key player in the mitotic spindle checkpoint machinery that monitors proper segregation of sister chromatides during mitosis. It has been suggested that mutations in BUB1 may disrupt the spindle checkpoint and thereby cause chromosomal instability, which is a hallmark of solid tumors including those from the breast. From a series of breast carcinomas we selected 20 cases with genomic instability, as scored by Comparative Genome Hybridization (CGH), and without somatic TP53 (p53) mutations, and sequenced the entire coding region of the BUB1 gene. Two different constitutional sequence variants were found; a base substitution in exon 5, c.481G>A (CAG>CAA, a synonymous change encoding Gln144) in two samples, and a base substitution 8 bp upstream of exon 10, c.1007-8T>C in two other samples. No somatic mutations were detected. These results indicate that genomic instability scored as copy number alterations by CGH in TP53 wild type breast carcinomas is not caused by somatic mutations in the BUB1 gene.
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PMID:BUB1 infrequently mutated in human breast carcinomas. 1451 64

Cyclin E overexpression occurs in a subset of endometrial carcinomas (ECs), but the molecular mechanisms underlying this alteration remain to be established. The present study has analysed amplification of the cyclin E gene (CCNE) and mutation in hCDC4, the gene coding for the F-box protein, which tags phosphorylated cyclin E for proteosomal degradation, to ascertain whether these alterations might be responsible for cyclin E overexpression in ECs. Cyclin E and p53 expression was studied by immunohistochemistry in eight atypical endometrial hyperplasias (AEHs), 51 endometrioid endometrial carcinomas (EECs), and 22 non-endometrioid endometrial carcinomas (NEECs). CCNE amplification was analysed by fluorescence in situ hybridization (FISH). Mutations in exons 2-11 of the hCDC4 gene were screened by PCR-SSCP-sequencing. Finally, the polymorphic marker D4S1610 was used to assess loss of heterozygosity (LOH) in the hCDC4 gene. Cyclin E overexpression was found in 26/81 (32%) cases and was associated with the histological type of the lesion, since it was not found in any AEHs but was present in 27% of EECs and 54.5% of NEECs (p=0.035). Cyclin E overexpression was associated with histological grade (p=0.011) and p53 immunostaining in EECs (p=0.033). CCNE amplification was found in 6 of 37 (16%) ECs examined. There was a significant association between CCNE amplification and the histological type of the lesion, since five (83%) of the six cases with amplification were NEECs (p=0.008). One EEC harboured an hCDC4 mutation: a CGA to CAA (Arg/Gln) change at codon 479. In addition, D4S1610 LOH was found in 7 of 23 (30%) informative cases analysed, but no correlation with cyclin E overexpression was found. However, the tumour with hCDC4 mutation also showed LOH. This is the first study demonstrating that cyclin E overexpression is associated with gene amplification in ECs, these alterations being more frequent in NEECs. Although hCDC4 exhibits a low mutation frequency in ECs overexpressing cyclin E, it seems to function as a tumour suppressor gene that is involved in endometrial carcinogenesis.
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PMID:Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma. 1464 62


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