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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumor suppressor genes p53, Rb, and DCC were studied in five human oral cancer cell lines (FaDu, SCC-4, HEp-2, 1483, and OEC-M1) and in primary normal human oral keratinocytes (NHOK). All tested cancer lines had similar amount of p53 messages to normal cells, but the cancer lines FaDu and SCC-4 contained significantly higher p53 protein levels than did the normal counterpart. Sequencing p53 cDNA for these cancer cells showed point mutations: In the FaDu cell line, a mutation of CGG to CTG occurred at codon 248; and in the SCC-4 cell line, a mutation of CCC to TCC occurred at codon 151. The HEp-2 and 1483 cancer lines translated very low levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations. Southern and Northern analyses revealed that these cell lines harbored HPV-18 DNA and expressed the viral E6/E7 protein. The OEC-M1 line showed different restriction fragment length polymorphism for the p53 gene compared with other cells, and did not express p53. All oral cancer cell lines except the OEC-M1 cells expressed both phosphorylated and hypophosphorylated Rb proteins. Further, the OEC-M1 line expressed smaller sized hypophosphorylated Rb proteins compared with normal cells. Unlike the other cancer lines, the HEp-2 and OEC-M1 lines also did not contain DCC mRNAs. These data indicate that "high risk" HPV infections and mutations of p53, Rb, and DCC genes are frequently found in oral cancer cells and may be associated with oral cancer.
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PMID:State of p53, Rb and DCC tumor suppressor genes in human oral cancer cell lines. 823 12

A nonisotopic screening method based on single-strand DNA conformation analysis (SSCA) was established for the identification of p53 gene alterations in achieved tissue samples. The sensitivity of this approach was validated by testing mutations previously identified by direct sequencing. Applying this assay, 40 samples of formalin-fixed, paraffin-embedded tumors, including 33 gastrointestinal carcinoids and seven endocrine pancreatic tumors, were screened. Only one mutation (codon 283, CGC to CCC) was identified in a single clinically benign rectal carcinoid. This mutation occurred during the development of the tumor and was accompanied by loss of the wild-type gene. Our data indicate, that, in contrast to gastrointestinal carcinomas, alterations of the p53 gene are infrequent events in the development of gastrointestinal and pancreatic carcinoids. In addition, there was no evidence for the involvement of p53 in the malignant metastatic progression of carcinoids.
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PMID:Identification of p53 gene mutations in gastrointestinal and pancreatic carcinoids by nonradioisotopic SSCA. 828 25

A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.
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PMID:Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations. 841 23

p53 gene which is known as a tumor suppressor gene locates in chromosome 17p and has a polymorphism at codon 72 (Arginine CGC-->Proline CCC). In this study, we examined the frequency of polymorphism and of heterozygosity in Japanese, and the loss of p53 gene in brain tumor tissues of the patients with heterozygosity using a novel method. The frequencies of heterozygosity, arginine type, proline type were 43%, 42% and 15%, respectively. Heterozygosity was observed in 15 out of 32 patients with brain tumors and loss of heterozygosity (LOH) in these 15 cases was demonstrated in 40%. Although we are not certain whether LOH of p53 region is inevitable process of oncogenesis of some brain tumors, some false negative results may occur. This quick technique requires small amount of samples and no radioactive isotope, therefore, can be applied to detect mutation and LOH occurred in p53 region in terms of the genesis and progression of human neoplasms.
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PMID:[Detection of codon 72 polymorphism of p53 gene from blood and loss of heterozygosity in brain tumors using polymerase chain reaction]. 847 53

Non-familial human adrenocortical adenomas and carcinomas were screened for mutations in exons 5-8 of the p53 tumor suppressor gene by single-strand-conformation-polymorphism (SSCP) analysis, followed by direct sequencing of PCR-amplified DNA. Point mutations in codons 12, 13 and 61 in H-ras, K-ras and N-ras proto-oncogenes were similarly assessed by direct DNA sequencing. Three out of 15 primary adrenocortical carcinomas (20%) contained a mis-sense point mutation in the conserved regions (exons 5 and 8) of the p53 gene. Mutations were located in codon 157 (GTC-->TTC; Val-->Phe), codon 163 (TAC-->AAC; Tyr-->Asn), and codon 273 (CGT-->TGT; Arg-->Cys). The mutation in codon 157 was detected in the primary tumor as well as in brain and lymph-node metastases. Among 18 adrenocortical adenomas, there was only a single non-miscoding mutation in codon 295 (CCT-->CCC; Pro-->Pro). These data suggest that mutational inactivation of the p53 gene occurs in a minority (20%) of sporadic adrenocortical carcinomas and that these mutations constitute a late event in the multi-step process of malignant transformation. No ras mutations were detected in any of these tumors, suggesting that these genes are not involved in the development of tumors originating from the adrenal cortex.
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PMID:p53 mutations in sporadic adrenocortical tumors. 850 16

The p53 tumor suppressor gene is often mutated in various human cancers and a common polymorphism is known at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). Association of this polymorphism with any human cancer susceptibility has yet to be clarified. We have conducted a case-control study in Japan on the distribution of the three genotypes with 191 lung cancer patients, 152 control patients with non-cancerous pulmonary diseases and 115 colorectal cancer patients. The genotypes were examined by PCR using DNA samples from peripheral blood lymphocytes. Frequency distributions of the three genotypes were quite comparable with each other among groups, with allelic frequencies of approximately 60% for arginine and 40% for proline. The genotypic frequencies in lung cancer patients, however, were largely different between smokers and non-smokers (chi 2 = 13.5, df = 2, P < 0.001). Compared with the control and colorectal cancer patients a significant difference in genotypic frequency was observed only in non-smoker lung cancers (chi 2 = 10.9, df = 2, P < 0.01), with an excess of Arg/Arg homozygotes and a deficit of Arg/Pro heterozygotes. Our present data suggest that the p53 polymorphism affects the risk of lung cancer unrelated to smoking.
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PMID:Analysis of a germ line polymorphism of the p53 gene in lung cancer patients; discrete results with smoking history. 862 47

Mutations in p53, a tumor suppressor gene, are one of the most common genetic lesions of human cancers. The relationship between p53 gene mutation and ultraviolet (UV) light has been demonstrated in skin cancers of sun-exposed sites. In this study, genomic DNA from 12 skin cancers was screened for mutations in exons 5 to 9 of this gene using the polymerase chain reaction--single strange configuration polymorphism (PCR-SSCP) analysis followed by DNA sequencing. DNA samples were obtained from 8 basal cell carcinomas (BCCs): 1 from an organoid nevus, 1 from a patient with basal cell nevus syndrome, 1 from a patient with xeroderma pigmentosum, and 1 from a recurrent and 4 from primary sporadic lesions on actinic damaged skin, and from 4 squamous cell carcinomas (SCCs): 1 from a burn scar, 1 from a patient with epidermodysplasia verruciformis, and 2 from actinic keratosis. Mutation of the p53 gene was detected in only 1 case of SCC which had arisen from actinic keratosis. The mutation occurred at codon 159 in exon 5 with a GCC to CCC base-pair substitution resulting in an amino acid change of alanine to proline. This mutation does not correspond to results of UV mutagenesis studies reported in the literature. Our findings imply that, although p53 gene mutation and UV exposure play an important role in the carcinogenesis of some skin cancers, they are not crucial, especially in skin cancers that develop from underlying skin disorders.
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PMID:p53 gene mutations in skin cancers with underlying disorders. 866 19

Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG --> AGT (Arg --> Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT --> AAA (Asn --> Cys) transversion at codon 200 in TONG/HCC, an AAG --> GAG (Lys --> Glu) transition at codon 139 in HCC-T, a CAT --> CGT (His --> Arg) transition at codon 214 in SC4, and a CCC --> CTC (Pro --> Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.
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PMID:Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. 877 41

Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners. p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specific mutational hot spot with the exception of a single study in which 31% of squamous cell and large cell lung cancers from uranium miners showed a p53 codon 249 AGGarg --> ATGmet mutation. Although the results of laboratory studies indicate that double-strand breaks and deletions are the principal genetic alterations caused by alpha-particles, uncertainty still prevails in the description of DNA damage in radon-associated human lung cancer. In the present study, we have evaluated the mutability of p53 codons 249 and 250 to alpha-particles in normal human bronchial epithelial (NHBE) cells using a highly sensitive genotypic mutation assay. Exposure of NHBE cells to a total dose of 4 Gy (equivalent to approximately 1460 working level months in uranium mining) of high LET alpha-radiation induced codon 249 AGG --> AAG transitions and codon 250 CCC --> ACC transversions with absolute mutation frequencies of 3.6 x 10(-7) and 3.8 x 10(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer.
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PMID:Radon and lung carcinogenesis: mutability of p53 codons 249 and 250 to 238Pu alpha-particles in human bronchial epithelial cells. 905 98

Several polymorphic genes have been reported to be possibly involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in human populations, and the null genotype has been reported to be a risk factor for developing lung carcinoma. A germline polymorphism of p53 with a single-base change at codon 72 that causes an amino acid replacement of arginine (Arg; CGC) by proline (PRO; CCC) has also been reported to be associated with cancer susceptibility in a Japanese population. Both polymorphisms were genotyped by PCR in a northwestern Mediterranean healthy population (n = 147) and in a group of lung cancer patients (n = 139). The results showed that the frequency of the GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51]. The histological subtypes most clearly modified were small cell carcinoma (OR, 1.89; CI, 0.97-3.65) and adenocarcinoma (OR, 1.93; CI, 0.90-4.14). The null GSTM1 genotype was more frequent among those cancer patients who were medium/ light smokers (< or = 50 pack-years) and in those who showed an onset of the disease at a more advanced age. The study of the p53 polymorphism in the healthy population showed allele frequencies of 0.79 (Arg) and 0.21 (Pro). The frequencies found in the lung cancer patients were statistically similar. Both polymorphisms were studied together, and the relative risk of the combination null GSTM1 and Pro/Pro or Arg/Pro genotypes was calculated taking the combination of GTSM1 + together with Arq/Arg as a baseline. The OR found (1.97; CI, 1.03-3.73) suggests that the Pro allele of the p53 germline polymorphism may slightly increase the risk fo the GSTM1 null genotype among smokers.
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PMID:Glutathione-S-Transferase M1 and codon 72 p53 polymorphisms in a northwestern Mediterranean population and their relation to lung cancer susceptibility. 916 98


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