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

We have examined 35 epidermal tumors induced in mice of four different strains by chronic exposure to ultraviolet B radiation for the presence of aberrations in the p53 tumor suppressor gene. Polymerase chain reaction products from p53 exons 5 to 8 were screened by single-strand conformation polymorphism analysis and sequencing. Base substitutions were found in seven tumors (20%). All mutations occurred at dipyrimidine sequences; most frequent were C-->T single base and CC-->TT tandem transitions suggesting the involvement of UV radiation in the genesis of the mutations. Three base substitutions were located at codon 148, and all dipyrimidine-derived mutations occurred at sites where the sequence is present in the nontranscribed DNA strand, indicating some site and strand specificity of the ultraviolet B-induced p53 mutations.
 ...
PMID:Carcinogen-specific mutational pattern in the p53 gene in ultraviolet B radiation-induced squamous cell carcinomas of mouse skin. 142 88

In human lung cancers, alterations of both a dominant oncogene (ras) and a tumor suppressor gene (p53) have been identified. Polymerase chain reaction (PCR) analysis of mRNA was used to amplify the c-Ki-ras-2 and p53 genes from Syrian golden hamsters. The PCR products were confirmed by predicted-size analysis, probing with nonradioactive (biotin-labeled) oligonucleotides, and direct sequencing. Lung tumors were produced in hamsters by repeated injections of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Of six tumors examined, three (50%) had mutations in codon 12 of Ki-ras. Examination of the conserved regions of p53 revealed no mutations. We conclude that NNK-induced carcinogenesis in the hamster results in characteristic alterations of Ki-ras but may not necessarily involve the p53 gene.
 ...
PMID:Mutational analysis of a dominant oncogene (c-Ki-ras-2) and a tumor suppressor gene (p53) in hamster lung tumorigenesis. 144 20

This study was undertaken to analyze the effect of wild-type p53 transfection on the growth potential of a human lung cancer cell line Hut292DM expressing endogenous wild-type p53. Transfection efficiencies obtained with either the wild-type or a mutant p53 complementary DNA revealed a significant decrease in the number of colonies obtained with the wild-type p53 as compared to the mutant p53 complementary DNA (27%) or control vector DNA only (20%), suggesting that wild-type p53 inhibited the growth of Hut292DM cells. A series of wild-type and mutant p53 transfection clones were then analyzed for the presence and expression of the exogenous p53 gene. Polymerase chain reaction amplification revealed that 98% of mutant p53 transfection clones analyzed contained the exogenous p53 gene as opposed to 47% for wild-type p53 clones. The majority of mutant p53 clones expressed high levels of exogenous p53 mRNA and protein as analyzed by Northern and Western blots, respectively. In contrast, all wild-type p53 clones analyzed failed to express exogenous p53 mRNA transcript or protein of a normal size. Aberrant-size p53 mRNA was detected in two wild-type p53 clones (X833.W2 and W18), and Western blot analysis revealed that these clones expressed truncated p53 proteins (M(r) 45,000 and 33,000 respectively). No difference in proliferation rates in vitro or in tumorigenic potential in nude mice were observed between mutant p53 clones or control cell lines. In contrast, a wild-type p53 clone (X833.W2) exhibited a significantly reduced tumorigenic potential in nude mice, whereas its in vitro proliferation rate was comparable to parental Hut292DM cells. The data indicate that exogenous expression of wild-type p53 is incompatible with Hut292DM lung cancer cell proliferation in vitro and suggest that p53-mediated growth control in vitro and in vivo may be dissociated and exerted by separate domains of the p53 protein.
 ...
PMID:Growth suppression mediated by transfection of p53 in Hut292DM human lung cancer cells expressing endogenous wild-type p53 protein. 145 87

Alterations in the p53 tumor suppressor gene and Epstein-Barr virus status were investigated in 15 nasopharyngeal carcinoma (NPC) biopsies, 4 xenografts, and 2 cell lines from the Cantonese region of southern China. One other established NPC cell line obtained from a northern Chinese patient was also studied. Restriction fragment length polymorphism analysis revealed a loss of heterozygosity for chromosome 17p, where the p53 gene resides, in only one of 15 NPC biopsies. Polymerase chain reaction-single-stranded conformational polymorphism analysis and direct sequencing failed to detect sequence alterations in exons 5 through 8 of the p53 gene in the 15 tumors and in the 4 NPC xenografts, all of which tested positive for Epstein-Barr virus. In contrast, the 3 NPC cell lines were all negative for Epstein-Barr virus and contained G----C transversions in the p53 gene, with cell lines CNE-1 and CNE-2 harboring identical AGA (arginine) to ACA (threonine) changes at codon 280. These results suggest that p53 inactivation is not a necessary component of nasopharyngeal carcinogenesis in Cantonese but may be important in the establishment of cell lines derived from these tumors.
 ...
PMID:Absence of p53 gene mutations in primary nasopharyngeal carcinomas. 151 42

Recent studies have demonstrated that families with the Li-Fraumeni syndrome carry inherited point mutations of the p53 gene. In the present study 25 families with strong histories of breast cancer were screened for the presence of such mutations. Polymerase chain reaction products of exons 5-9 of the p53 gene were examined by single-stranded conformational polymorphism analysis and, in addition, exon 7 was further screened by direct sequencing. No mutations were detected in constitutive DNA by either method. These results indicate that familial breast cancer does not usually result from germline point mutations in the p53 gene.
 ...
PMID:No evidence for germline mutations in exons 5-9 of the p53 gene in 25 breast cancer families. 157 Jan 51

Two prostate carcinoma cell lines, DU-145 and PC-3, were examined for abnormalities in the retinoblastoma (Rb) and the p53 putative tumor suppressor genes. We found an abnormal Rb gene product in DU-145 using Western blot analysis. Polymerase chain reaction amplification followed by direct DNA sequencing demonstrated a base substitution mutation that generates a stop codon in exon 21. On Northern, Southern, and Western blot analysis, the p53 gene and its product appear to be normal in DU-145. PC-3, however, failed to demonstrate expression of either the p53 transcript on Northern blot analysis or the p53 protein on Western blot analysis, while the Rb gene products appeared to be normal on both Northern and Western blot analysis. This work extends the correlation between abnormal expression of putative tumor suppressor genes and human malignancies.
 ...
PMID:Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes. 198 44

To elucidate the role of p53 in colon tumorigenesis in mice, we examined allele loss and mutational alteration of the p53 gene in colon tumors induced by 1,2-dimethylhydrazine (DMH) in F1 hybrid mice. Intragenic polymorphism of the p53 gene among parental strains enabled us to assess allele loss of the p53 gene and also to determine parental origin of mutated and/or lost alleles. Allele loss was detected in two of 163 tumors heterozygous for the p53 gene. Polymerase chain reaction-single-strand conformation polymorphism analysis of p53 exons 5-8 revealed 33 mutations in 20 of 182 colon tumors, the incidence being lower than that in human colon cancers. The majority of these mutations were of transition type: G:A transitions at non-CpG sites were most prevalent, while those at CpG sites were less common. Distribution of the mutations along p53 amino acid sequence revealed a difference in the location of 'hot spots' between mice and humans. Incidence of p53 alterations did not differ among alleles of different parental origins, suggesting that genetic changes in DMH-induced mouse colon tumors had occurred independently of parental origin and DMH susceptibility. Detailed analysis of p53 mutations on each allele revealed intratumoral heterogeneity in mouse colon tumors. The low incidence of p53 mutations and rare allele loss suggest that p53 alteration plays only a minor role in colon tumorigenesis in mice.
 ...
PMID:Mutational and LOH analyses of p53 alleles in colon tumors induced by 1,2-dimethylhydrazine in F1 hybrid mice. 758 83

A series of eight oral epithelial cell lines derived from untreated human oral squamous cell carcinomas, which had arisen in patients with different tobacco histories, were examined for the presence of human papillomavirus (HPV) DNA, expression of stable p53 protein and p53 point mutation. Polymerase chain reaction (PCR)-based screening, but not Southern blot analysis, showed HPV-16 early region sequences to be present at low copy number (< 1 copy per cell) in two cell lines at early passage (3-5) in vitro (H400, T45), implying that only subpopulations of cells harboured viral DNA. HPV sequences were undetectable in cells at later passage (12-15), suggesting that viral sequences had been lost during growth in vitro, or that negative selection of HPV-containing cells had occurred. High levels of p53 were detected in the two HPV-positive cell lines and in three others (H103, H314, H357) by Western blotting, suggesting expression of mutant (stable) p53 molecules. A sixth cell line (H157) expressed a truncated p53. Sequence analysis of exons 2-11 of the p53 gene revealed missense mutations in six cell lines, one of which (H413) did not result in high levels of protein, and nonsense mutations in the remaining two cell lines (H157, H376). The results suggest that p53 mutation is a frequent genetic event in oral cancer. In addition, the expression of mutant p53 in oral cancer cells does not preclude a papillomaviral aetiology for these tumours. Analysis of p53 expression alone may result in underestimation of the frequency of p53 mutations in human cancers.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Presence of human papillomavirus sequences in tumour-derived human oral keratinocytes expressing mutant p53. 763 86

Mutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.
 ...
PMID:Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples. 765 83

Denaturing gradient gel electrophoresis (DGGE) separates (DNA) molecules based on their sequence. Using the proper conditions, all base-pair substitutions can be resolved from the wild-type sequence using DGGE. Polymerase chain reaction (PCR) permits rapid amplification of a given region of the genome. In this paper, we demonstrate the utility of DGGE combined with PCR for mutation analysis by presenting different examples: (i) analysis of mouse p53 cDNA for mutations, (ii) simultaneous analysis of thousands of 4NQO-induced mutants for mutations in HPRT exon 3, (iii) examination of the fidelity of the thermostable DNA polymerase isolated from Pyrococcus furiosus (Pfu), (iv) purification of mutant DNA from contaminating wild-type DNA from mouse spleenic T-cell clones.
 ...
PMID:Mutational analysis using denaturing gradient gel electrophoresis and PCR. 768 54


1 2 3 4 5 6 7 8 9 10 Next >>