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)

Recently, Frey (Cytometry 17:310-318, 1994) demonstrated that TO-PRO-3 iodide (TP3) can be excited indirectly by a 488 nm laser line through energy transfer by propidium iodide (PI). In the present study, we investigated whether PI-TP3 energy transfer can help to overcome spectral cross talk problems associated with the combined use of fluorescein isothiocyanate (FITC), R-phycoerythrin (PE), and PI. Mixtures of keratin 8/18 FITC-labeled, keratin 8/18-PE-labeled, and unlabeled MCF-7 breast carcinoma cells were prepared and stained for DNA with PI (100 microM). The effect of adding a range of TP3 concentrations (0.001 to 16 microM) to these mixtures was evaluated. The combined use of PI and TP3 was further evaluated using mixtures of unlabeled and p53 FITC-labeled COV362.cl4 ovarian cancer cells and mixtures of unlabeled and p53 FITC-labeled COV362.cl4 cells and peripheral blood lymphocytes (PBL), additionally stained for keratin 8/18 (PE). Finally, a human ovarian ascites tumor specimen was triple-stained for keratin 8/18 (PE), vimentin (FITC) and DNA or keratin 8/18 (PE), PCNA (FITC) and DNA. Addition of TP3 allowed complete correction for spectral cross talk of PE/PI into the green fluorescence detector (FL1). Only minimal (FL1 - %FL2) compensation was required at a TP3 concentration of 2.0 microM in the presence of PI (100 microM). The PI spectral cross talk into the orange fluorescence detector (FL2) was reduced by about 50% using the same photomultiplier (PMT) settings. Although addition of TP3 reduced the signal-to-background ratio by about 30%, the advantage gained through full compensation for spectral cross talk resulted in an improved discrimination of p53-positive and -negative subpopulations in a mixture of human PBL and COV362.cl4 cells. Furthermore, vimentin-negative and PCNA-negative cells were better resolved in a human DNA-aneuploid ovarian ascites tumor after staining the DNA with PI/TP3, rather than with PI alone. We conclude that the addition of TP3 to PI improves the combined measurement by single-laser flow cytometry of DNA-ploidy and antigen expression in heterogenous clinical samples.
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PMID:Improved single laser measurement of two cellular antigens and DNA-ploidy by the combined use of propidium iodide and TO-PRO-3 iodide. 926 54

Thymic epithelial tumours are broadly classified into thymomas and thymic carcinomas. Although both tumours occasionally show invasive growth, they exhibit different clinical and biological findings. The oncogene and anti-oncogene in thymic epithelial tumours have not been evaluated fully. We investigated the expression of p53 protein by immunohistochemical analysis using the anti-p53 polyclonal antibody (CM-1) in 17 thymomas and 19 thymic carcinomas. We also examined p53 gene (exon 5-8) mutation in 18 thymic carcinomas by using polymerase chain reaction-single-strand conformation polymorphism methods and direct sequencing. Of the thymoma cases, only one invasive thymoma showed focal nuclear staining. Fourteen of the 19 thymic carcinomas (74%) showed nuclear staining. Point mutations of the p53 gene were recognized in only 2 of the 18 thymic carcinomas (11%). One was the mutation C to T transition in the first letter of codon 222 in exon 6, which results in the amino acid substitution from proline to serine. Another was a silent mutation. p53 protein accumulation is highly frequent in thymic carcinomas but not in thymomas, and gene mutation is uncommon in thymic carcinomas.
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PMID:High frequency of p53 protein expression in thymic carcinoma but not in thymoma. 937 84

The polymorphism of p53 gene at codon 72 consisting of either arginine (Arg)- or proline (Pro)-encoded allele is suggested to be associated with the susceptibility of tobacco-related lung cancer. In this study we examined the polymorphism of 224 non-small cell lung cancer (NSCLC) patients and that of 303 control persons with a polymerase chain reaction method and found that Pro-allele carriers were significantly more frequent in those patients who smoked and were affected at a younger age (<65) (P<0.05). We also investigated whether the mutational alterations of this gene could be influenced by the genotype. The overall mutation rate of 114 NSCLC patients examined with a single-strand conformation polymorphism method was 31%, which agreed with previous reports. However, the mutation rate was significantly increased in those patients who smoked and were affected at a younger age (<65) (P<0.05). Although the Pro-allele carriers among the smoker patients showed higher mutation rate than the Arg/Arg homozygotes, the difference between the genotypes had marginal significance (0.1<P<0.05) and was statistically insignificant, if the study was confined to younger patients. Thus, the present data cannot confirm a possible association of the p53 polymorphism with its mutation rate regarding smoking-related lung cancer.
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PMID:Correlation of the mutation of p53 gene and the polymorphism at codon 72 in smoking-related non-small cell lung cancer patients. 947 95

We describe two Li-Fraumeni syndrome families. Family A was remarkable for two early childhood cases of adrenocortical tumours, family B for a high incidence of many characteristic cancers, including a childhood case of choroid plexus tumour. Using direct sequencing, we analysed exons 5-9 of the p53 gene in constitutional DNA of individuals from both families and found two novel germline mutations in exon 5. In family A, we detected a point substitution in codon 138 (GCC to CCC), which resulted in the replacement of the alanine by a proline residue. Family B harboured a single-base pair deletion in codon 178 (CAC to -AC), resulting in a frameshift and premature chain termination. Three out of six tumours examined from both families, a renal cell carcinoma, a rhabdomyosarcoma and a breast cancer, showed loss of heterozygosity and contained only the mutant p53 allele. The remaining three neoplasms, both adrenocortical tumours and the choroid plexus tumour retained heterozygosity. Immunohistochemistry with anti-p53 antibody confirmed accumulation of p53 protein in tumours with loss of heterozygosity, while the remaining tumours were p53 negative. These results support the view that complete loss of activity of the wild-type p53 need not be the initial event in the formation of all tumours in Li-Fraumeni individuals.
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PMID:Two Li-Fraumeni syndrome families with novel germline p53 mutations: loss of the wild-type p53 allele in only 50% of tumours. 956 35

The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.
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PMID:Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. 985 89

Chondrosarcoma is a primary bone tumor that has several different grades and variants. We evaluated 48 chondrosarcomas for p53 overexpression and p53 mutations. p53 expression was evaluated with immunohistochemistry using monoclonal antibodies PAb421, PAb1801, and PAb240. p53 mutations were identified with single-strand conformational polymorphism (SSCP) and DNA sequencing in selected cases. Immunohistochemistry revealed nuclear staining with PAb421 and PAb1801 in the spindle cell portion of one dedifferentiated chondrosarcoma. SSCP analysis was abnormal only in the case with positive immunostaining and localized the mutation to exons 7 and 8. DNA sequence analysis identified a point mutation of G to C in codon 276, resulting in an amino acid substitution of proline for alanine. This point mutation has been reported previously in other tumors but not in chondrosarcoma. Assimilation of our results with previous studies suggests that p53 mutations are present in a minority of chondrosarcomas but when present, are in higher grade chondrosarcomas and their variants.
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PMID:p53 mutations in chondrosarcoma. 964 35

The prognostic value of the mutation of the p53 tumor suppressor gene in non-small cell lung carcinomas (NSCLC) is controversial and a polymorphism of the p53 gene at codon 72 consisting of two alleles, arginine (Arg) and proline (Pro), has been reported to be associated with the incidence of smoking-related NSCLC. We have studied 67 cases of NSCLC in relation to the mutation of the p53 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism and 178 cases in relation to the polymorphism of the gene by PCR using allele-specific primers. The genetic alterations of the p53 gene (from exons 5 to 9) were found in 34% of the patients. Frequent mutations were observed among younger patients (less than 65 years old), however, there is no significant correlation of the mutation with smoking history, histopathological types, clinical stages or prognosis. We observed that Arg/Arg homozygotes were frequently found in non-smoking patients with NSCLC but Arg/Pro heterozygotes were infrequent in the group. There was no significant association of the polymorphic alleles with histopathological types, clinical stages or prognosis. Thus, the polymorphism of the p53 gene affects the predisposition of non-smokers to NSCLC, but the alteration of the p53 gene is independent of tumor progression and histopathology.
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PMID:Prognostic value of mutations and a germ line polymorphism of the p53 gene in non-small cell lung carcinoma: association with clinicopathological features. 965 98

Human papillomavirus (HPV)-16 and -18 encode E6 oncoprotein, which binds to and induces degradation of the tumor suppressor protein p53. A common polymorphism of p53, encoding either proline or arginine at position 72, affects the susceptibility of p53 to E6-mediated degradation in vivo; Caucasian women homozygous for arginine 72 reportedly are about seven times more susceptible to HPV-associated carcinoma of the cervix than heterozygotes. To examine whether arginine 72 could be a risk factor for HPV-associated cervical carcinomas in the Japanese population, we used the same PCR-based assay to analyze p53 genotypes of HPV-positive invasive cervical carcinomas from 103 Japanese women versus 110 control samples. Inasmuch as we detected no significant difference in the frequencies of proline or arginine alleles between the two groups, p53 polymorphism at residue 72 does not seem to be involved in the development of HPV-associated cervical carcinomas in women of Japanese ethnicity.
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PMID:No evidence of correlation between polymorphism at codon 72 of p53 and risk of cervical cancer in Japanese patients with human papillomavirus 16/18 infection. 978 6

The wild-type p53 protein exhibits a common polymorphism at amino acid 72, resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg) at this position. Despite the difference that this change makes in the primary structure of the protein resulting in a difference in migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no differences in the biochemical or biological characteristics of these wild-type p53 variants have been reported. We have recently shown that p53Arg is significantly more susceptible than p53Pro to the degradation induced by human papillomavirus (HPV) E6 protein. Moreover, this may result in an increased susceptibility to HPV-induced tumors in homozygous p53Arg individuals. In further investigating the characteristics of these p53 variants, we now show that both forms are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner. However, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells. These observations may have implications for the development of cancers which harbor wild-type p53 sequences and possibly for the ability of such tumors to respond to therapy, depending on their p53 genotype.
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PMID:Two polymorphic variants of wild-type p53 differ biochemically and biologically. 989 Oct 44

The potential association of distinct polymorphisms of the tumor suppressor gene p53 with an increased susceptibility to malignant transformation has been reported for various cancer entities. Most recently, p53 protein containing an arginine residue in codon 72 was shown to be more effectively degraded by the E6 oncoprotein of human papillomavirus (HPV) than the corresponding proline isoform in cervical carcinoma cells. Additionally, a seven times higher risk of cervical cancer for Arg homozygotes was suggested. We set out to confirm this allele-specific predisposition on a larger population, comprising 87 cervical cancer and 151 normal control samples. However, there was no significant difference in the observed frequencies of homozygous Arg genotypes in cervical cancer patients (52.8%) and normal controls (55.7%). Furthermore, the prevalence of the Arg/Arg allelotype did not vary between HPV+ (n = 75) and HPV- (n = 12) carcinoma samples. Thus, our investigation of a larger set of clinical samples does not support the proposed association of any polymorphic status of p53 at codon 72 with an elevated risk for cervical cancer.
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PMID:No evidence of p53 allele-specific predisposition in human papillomavirus-associated cervical cancer. 1002 83


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