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)

The growth of three non-tumorigenic human colonic adenoma cell lines, designated AA/C1, RG/C2 and RR/C1, was inhibited by low concentrations of transforming growth factor beta (TGF-beta) (0.05-0.5 ng ml-1). However, the growth of five human colon cancer cell lines under identical conditions was resistant to high concentrations of TGF-beta (2-10 ng ml-1). This is the first report of well-characterized premalignant human colonic cells showing sensitivity to TGF-beta. The TGF-beta-sensitive adenoma cell line AA/C1 was derived from a relatively large adenoma with a K-ras gene mutation and represents a relatively late-stage adenoma, indicating that loss of response to TGF-beta occurs at a relatively late stage in colorectal carcinogenesis and that the presence of a ras gene mutation does not necessarily confer resistance to TGF-beta. Of further interest, the RG/CZ cell line has a p53 mutation showing that p53 mutations do not necessarily lead to TGF-B insensitivity. Furthermore, in this paper we show that the conversion of the AA/C1 adenoma cell line to a tumorigenic phenotype [Williams et al., (1990) Cancer Res., 50, 4724] is accompanied by a reduced response to the growth-inhibitory effects of TGF-beta up to 10 ng ml-1. Reduced responsiveness to the inhibitory effects of TGF-beta may be an important event in the loss of growth control in colorectal carcinogenesis.
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PMID:Differential sensitivity of human colonic adenoma and carcinoma cells to transforming growth factor beta (TGF-beta): conversion of an adenoma cell line to a tumorigenic phenotype is accompanied by a reduced response to the inhibitory effects of TGF-beta. 188 18

Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.
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PMID:p53 mutations in human cancers. 190 40

Examples of practical approaches to molecular epidemiology of human cancer are described. Biomarkers of carcinogen exposure or inherited host factors for cancer susceptibility are discussed. Major advances have been made in the detection of carcinogenmacromolecular adducts through the use of high performance liquid chromatography, immunoaffinity chromatography, the 32P-postlabeling assay, enzyme immunoassays, gas chromatography/mass spectroscopy and synchronous spectrophotofluorimetry. The polycyclic aromatic hydrocarbon-DNA adducts are the most extensively studied in this field and together with antibodies to these adducts found in human serum, they have become useful indicators of exposure to carcinogens. Assays for various kinds of alkyl-DNA adducts have also been developed and the presence of these adducts have been documented in human tissues. Carcinogen-protein adducts have proven to be useful molecular dosimeters of carcinogen exposure. For example, 4-aminobiphenyl hemoglobin adducts are highly correlated with exposure to tobacco smoke. The study of the molecular aspects of interindividual differences in the metabolism and activation of xenobiotics and other genetic markers [DNA-restriction fragment length polymorphisms (RFLPs), mutations, and functional loss of specific genes in carcinogenesis] is an emerging new field that is discussed in the context of genetic susceptibility to cancer. The cytochrome P450 phenotypes and acetylation phenotype are examples of genetic markers that indicate an individual's potential for metabolism of exogenous substances. Further, inherited genetic polymorphic markers, e.g., DNA-RFLPs at protooncogene loci (HRAS-1 and L-myc) have been examined in a case-control study of lung cancer. Data concerning mutations of protooncogenes (H-, K-, and N-RAS) and tumor suppressor genes (retinoblastoma and p53 genes) in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis.
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PMID:Biochemical and molecular epidemiology of cancer. 191 Jun 3

The p53 gene has been implicated as a tumour suppressor, with mutations occurring in many carcinomas, such as colon, breast and lung. We have sequenced exons 5, 7 and 8 containing conserved gene regions in the only available differentiated thyroid follicular carcinoma cell line and found a mutation at position 273, Arg----His, with no normal allele present. The same mutation was also present in DNA from the tumour of origin. However immunohistochemical analysis of 129 human thyroid tumours using a panel of p53 antibodies was unequivocally negative. Southern blotting in 20 cases failed to demonstrate any deletion or rearrangement, and direct genomic sequencing of 20 carcinomas showed normal DNA sequence for exons 5, 7 and 8. Thus p53 abnormalities may not be important in human thyroid carcinogenesis, in contrast to colon, breast and lung. However, the FTC 133 cell line was only established after 132 unsuccessful attempts with other differentiated thyroid follicular tumours. Since this line and the corresponding tumour of origin have a p53 mutation, we propose that p53 mutation may confer on thyroid follicular tumour cells the ability to grow in culture. This has potential applications for the future development of thyroid carcinoma cell lines.
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PMID:Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours. 192 34

Abnormality of tumor suppressor gene p53 is supposed to be associated deeply with colon carcinogenesis. We have examined the aberrant expression of the p53 protein in human colorectal cancer or adenomatous tissues immunohistochemically using monoclonal antibody PAb 1801. In microwave-fixed colorectal tissues, p53 was successfully detected in more than 60% of carcinomas. Specific signal for p53 was restricted in the nuclei of cancer cells, while no staining was observed in adjacent normal mucosa. The incidence of p53 expression in colorectal carcinomas was not affected by pathological features such as tumor size, histological grade, nor depth of invasion. In about 10% of colorectal adenomas, weak signal was detected in a few adenomatous glands. Heat shock protein of 72 kDa (HSP72), known to form complex with the mutant-type of p53 in tumor cells, was also detected immunohistochemically in 25% of p53-positive cases. In these cases, high incidence of lymphnodal or distant metastasis was observed, which suggests that expression of both p53 and HSP72 may indicated biological malignancy of the colorectal carcinomas.
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PMID:[Expression of P53 and heat shock protein in colorectal tumors: an immunohistochemical study]. 194 62

p53 protein was detected by immunohistochemistry in 42% of 52 colorectal adenocarcinomas. Positive tumours were significantly more frequent in the distal colon, and demonstrated a higher rate of cell proliferation. No correlation was found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient survival. The role of p53 in colorectal carcinogenesis is discussed with particular reference to differences between proximal and distal large bowel cancers.
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PMID:p53 in colorectal cancer: clinicopathological correlation and prognostic significance. 199 14

Recently, loss or inactivation of genes at specific chromosomal loci has been considered to be one of the important mechanisms during the development of human tumors. In order to identify tumor suppressor genes for gastric carcinoma, we performed restriction fragment length polymorphism analysis on 48 human gastric carcinomas. Allele losses were investigated for 14 specific loci on chromosomes 1, 5, 6, 7, 10, 11, 12, and 17. Loss of heterozygosity on chromosome 17p13.1 (p53 locus) was detected in 13 (68%) of 19 informative cases. Well-differentiated adenocarcinoma showed high frequencies of allele losses on chromosomes 5q (60%) and 17p (67%) in early cancers and on chromosomes 1q (67%), 5q (36%), 7p (33%), 7q (39%), and 17p (73%) in advanced cancers. In poorly differentiated adenocarcinomas, loss of heterozygosity was detected on chromosomes 1p (38%), 12q (31%), and 17p (60%). Allele losses on chromosomes 1q, 5q, and 7p were not detected in poorly differentiated adenocarcinoma, their frequencies being significantly different between the two histological types. These results suggest that allele loss on chromosome 17p is a common event in gastric carcinoma, regardless of histological type, and that allele loss on chromosome 5q may play a role in the carcinogenesis of well-differentiated adenocarcinoma. Additionally, allele losses on chromosomes 1q and 7p may be involved in the progression of well-differentiated adenocarcinoma.
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PMID:Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas. 203 30

Mutations of the p53 gene were investigated after tumor cell enrichment by cell sorting based on differences in DNA content and polymerase chain reaction single-strand conformation polymorphism analysis in 24 surgical specimens of primary gastric cancer. p53 mutations were detected in exons 4-8 in 64% (9 of 14) of aneuploid tumors but in none of 10 diploid tumors examined. Four of five tumors containing two or three aneuploid subpopulations showed the presence of p53 gene mutations. No correlation was found between the presence of p53 mutations and the degree of histological differentiation of tumors. These findings suggest that p53 gene mutations are related to DNA ploidy alterations as relatively late events of carcinogenesis in gastric cancer. The present method is highly sensitive for detection of genetic abnormalities and is applicable even when various kinds of nontumorous cells are present in tumor samples.
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PMID:Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. 203 45

Several types of human and animal tumors have been shown to carry mutations in the p53 gene. While the translation product of the wild type gene has tumor suppressor properties, mutant alleles of the gene produce proteins that can cooperate with other oncogene products in transforming cells. In this paper, evidence is presented indicating that a p53 gene mutation(s) occurs in foci of enzyme-altered hepatocytes induced by diethylnitrosamine in male Fisher-344 rats. The evidence was obtained by means of immunohistochemical and immunoblotting techniques, using antibodies directed against mutant forms of the p53 protein.
Carcinogenesis 1991 Jun
PMID:Expression of p53 mutant protein(s) in diethylnitrosamine-induced foci of enzyme-altered hepatocytes in male Fischer-344 rats. 204 96

The common malignancies apparently develop by a stepwise accumulation of gene alterations including oncogenes and suppressor genes. Point mutation or deletion might be an early event for carcinogenesis and tumor progression, while amplification of several oncogenes occur as a late event. Amplification of some oncogenes apparently relate with patient prognosis, i.e. erbB2 for breast, ovarian and gastric carcinomas, HST-1/INT-2 for esophageal and breast carcinomas, and N-myc for neuroblastoma. Although amplification of erbB1 is less common, its expression indicate poorer prognosis in patients with esophageal, gastric and bladder carcinomas. Combination analysis of the gene amplification and other gene alterations, such as p53 gene might provide more useful clinical informations for the postoperative management and prognosis of cancer patients.
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PMID:[Oncogene and patient prognosis]. 205 66


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