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)

Mutations of ras oncogene and multiple tumor suppressor genes p53, Rb and APC in esophageal epithelium of rhesus monkey fed with one dose of N-methyl-N-benzylnitrosamine (NMBzA 30mg/kg), which was found in high incidence areas of esophageal cancer in China, were analysed by PCR and direct sequencing. Mutation at codon 12 of Ha-ras gene was not found in esophageal epithelium of monkey fed with NMBzA. Some mutations of p53 gene were found in esophageal epithelium of monkey after being fed with NMBzA for 24-48 hours. Some mutation of Rb and APC were found in esophageal epithelium of monkey after being fed with NMBzA for 48 hours. The mutation fingerprints of these genes disappeared in esophageal epithelium of monkey after being fed with NMBzA for 5 days. The results demonstrated that chemical carcinogen NMBzA can induce mutations of multiple tumor suppressor genes in monkey (in vivo) and indicated that the alteration of tumor suppressor genes in the initial stage of carcinogenesis needs many hits by chemical carcinogen. These alterations of p53, Rb, APC genes were similar to the changes of these genes in some reported previously primary esophageal cancer.
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PMID:[Effect of NMBzA on the oncogene and multiple tumor suppressor genes in monkey esophageal epithelium]. 778 Nov 21

Little is known of the molecular changes that occur in germ cell tumors (GCT) of the testis. We studied three GCT cell lines and 44 tumors for loss of heterozygosity (LOH) of the tumor suppressor genes APC, MCC, DCC, RB, TP53, and WT-1. We observed that LOH occurred in 55% (21 of 38) of informative cases at DCC, in 28% (10 of 36) of informative cases at APC, in 23% (6 of 26) at MCC, in 30% (13 of 43) at RB, and in 27% (6 of 22) at WT-1. The LOH level in these tumors using anonymous primers mapping to the short and long arms of chromosome 19, which is cytogenetically normal in GCT, revealed LOH of 11 and 5%, respectively. We also observed a LOH of 22% in the TP53 gene, despite the fact that mutations in TP53 do not occur in testis cancer. Since a high frequency of LOH at DCC (18q21.3) occurs equally at all histological subsets in GCT, we conclude that the loss of the function of this gene is an early event in testicular GCTs. However, the observed LOH levels at APC/MCC (5q21), RB (13q14), and WT-1 (11p13) could represent a functional loss of the corresponding tumor suppressor gene in some GCTs or reflect the loss of sequences in the same general chromosome region but involving a different tumor suppressor locus. Therefore, detailed mapping of these chromosomes is required to define the precise locations of maximal LOH in testis cancer.
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PMID:Loss of heterozygosity of tumor suppressor genes in testis cancer. 779 15

Fascinating progress has been made in the past 2 years in our understanding of the genetic alterations associated with colorectal cancer predisposition and development. First, the genotype-phenotype relationship of the cancer susceptibility syndrome associated with familial adenomatous polyposis has been shown to depend on mutation type. Second, hereditary nonpolyposis colorectal cancer syndromes have been recognized as being frequently associated with a defect in the DNA mismatch-repair pathway. A gene on chromosome 2 called hMSH2, which demonstrates homology with the bacterial repair gene MutS, has been shown to be altered in some families with hereditary nonpolyposis colorectal cancer. A defect on chromosome 3 may act by impairing the same pathway. Genotyping of particular loci, termed microsatellite, provides an easy identification of tumors deficient in mismatch repair. Third, the mechanisms by which the inactivation of tumor-suppressor genes such as p53 and APC may contribute to the tumorigenic process have begun to be elucidated. These different discoveries will have important impacts in the prevention and management of colorectal carcinoma, one of the most frequent human cancers.
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PMID:Advances in the genetics and molecular biology of colorectal tumors. 780 42

Colorectal carcinomas demonstrate extensive molecular genetic alterations throughout the genome. The genetic changes in cancer of the colon and rectum are among the best understood of any common human cancer. The genetic abnormalities include both dominant-acting oncogenes (Ki-ras, c-src) and tumor-suppressor genes which undergo inactivation or loss (APC, DCC, p53). The evolution of the cancer is a complicated and multistep process. At the various steps of this phenomenon we can recognize specific molecular genetic alterations. These particular genetic changes may be useful as improved markers to predict those patients who have an aggressive cancer of the colon, with occult metastases or increased metastatic capability and this selection of patients could lead to improved surgical and medical management.
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PMID:The genetic basis of colorectal cancer--clinical implications. 785 69

Cell fusion experiments performed by Harris et al. informed that tumor suppressor genes are inactivated in malignant cells. Inactivation of tumor suppressor genes induced by genetic alteration such as point mutation and deletion leads to disturbance in the control of cell proliferation resulting in deregulated growth of normal cells. Recently, many challenges of scientists including clinicians trying to direct the studies of tumor suppressors toward cancer therapy have been stimulated. For that purpose, it is important to understand the molecular mechanism in which change of normal phenotypes into tumor take place. In this review, recent topics on tumor suppressors such as Rb, p53, Wt1, APC, NF1, s-Myc and H19 are included to discuss their significance and function.
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PMID:[Tumor suppressor genes]. 785 29

Mutation of the p53 gene and loss of heterozygosity of the p53, Rb, APC, and MCC genes were examined in 14 hepatocellular carcinomas (HCCs) diagnosed at the third department of internal medicine in Asahikawa Medical College. Mutations in the p53 gene were detected in 4 HCCs out of 14 (25%) using polymerase chain reaction-single strand conformational polymorphism. The sites of the mutations showed a random distribution from exon 6 to 8. No mutation was observed at codon 249, which has been considered as a mutational hot spot caused by aflatoxin B1. All of the mutations occurred at a G:C base pair site, while two mutations were C:G to T:A transitions and other two mutations were G:C to T:A transversions. Pathological examination showed that the 14 HCCs consisted of 7 moderately and 7 poorly differentiated HCCs. All of the 4 HCCs which showed mutations were poorly differentiated and the frequency of the mutations were 0% in moderately and 57% in poorly differentiated HCCs. Loss of heterozygosity of the p53, Rb and APC genes were examined in the 14 HCCs using restriction fragment length polymorphism analysis. Frequencies of the loss of the p53, Rb, APC, and MCC genes were 2 out of 7 informative cases (2/7), 1/6, 0/4, and 0/7, respectively. Frequency of loss of the p53 gene in four HCCs carrying a mutated p53 gene was 1/3. These data suggest that inactivation of the p53 gene is involved in human hepatocarcinogenesis, but the APC/MCC genes are not.
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PMID:[Aberrations of tumor suppressor genes in hepatocellular carcinomas]. 786 63

Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas (HCC) from southern Africa and Qidong in China. The objective of the present work was to test the hypothesis that exposure to aflatoxin B1 either alone or coincident with other environmental carcinogens might be associated with allelic losses occurring during development of human hepatocarcinogenesis in China. The HCCs were obtained from two different areas in China: Qidong, where exposure to hepatitis B virus (HBV) and aflatoxin B1 is high; and Beijing, where exposure to HBV is high but that of aflatoxin B1 is low. We analyzed the tumors for mutations in the p53 gene and loss of heterozygosity for the p53, Rb, and APC genes and at marker loci on chromosomes 4, 13, and 16. Frequencies of mutation, loss, and aberration (mutation and loss) of the p53 gene in 25 HCCs from Qidong were 60, 58, and 80%, respectively. The frequencies in 9 HCCs from Beijing were 56, 57, and 78%. However, the frequency of a G to T transversion at codon 249 in HCCs from Qidong and Beijing were 52 and 0%, respectively. These data indicate that mutation and/or loss of heterozygosity in the p53 gene, independent of the 249 mutation, play a critical role in the development of hepatitis B virus-associated HCCs in China. Loss of the Rb and APC genes was observed in 44 and 7% of HCCs from Qidong, respectively. Allelic losses on chromosome 4 and especially on chromosome 16 were frequent in HCCs from Qidong but were not observed in HCCs from Beijing, while loss of heterozygosity on chromosome 13 occurred at similar frequency in both Qidong and Beijing. These results show a distinct difference in the pattern of allelic losses between HCCs in Qidong and Beijing and suggest that aflatoxin B1 and/or other environmental carcinogens may contribute to this difference.
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PMID:Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. 806 70

Although it is widely accepted that tumor suppressor genes play an important role in the genesis and progression of human cancer, little is known about genetic events that accumulate during multistage lung carcinogenesis. Thus, to determine a subset of tumor suppressor genes that are involved in the genesis and progression of non-small cell lung carcinoma (NSCLC), 22 brain metastases and 23 stage I primary lung tumors were examined for allelic losses at 40 loci on 10 chromosomes including the loci of 5 tumor suppressor genes, APC, WT1, RB, p53, and DCC. The incidence of allelic losses on chromosomes 3p, 13q, and 17p was high (> 60%) in both primary tumors and brain metastases. In brain metastases, a high incidence of allelic losses (> 60%) was also observed at loci on chromosomes 2q, 18q, and 22q, and the incidence of allelic losses on these chromosomes in brain metastases was significantly higher than that in primary tumors (P < 0.05). In two cases of brain metastases with corresponding primary lung tumors, sequential accumulation of allelic losses during progression of primary lung tumors was observed on several chromosomes including chromosomes 2q and 18q. These results indicate that, besides loss of heterozygosity for chromosomes 3p, 13q, and 17p, loss of heterozygosity for chromosomes 2q, 18q, and 22q also occurs frequently in advanced NSCLCS. Thus, it is possible that loss of heterozygosity on chromosomes 2q, 18q, and 22q occurs late in the progression of NSCLC and/or causes phenotypic alterations of NSCLC cells into more aggressive ones.
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PMID:Frequent allelic losses on chromosomes 2q, 18q, and 22q in advanced non-small cell lung carcinoma. 792 10

The aim was to determine whether proton magnetic resonance spectroscopy (MRS) could grade human colorectal cells of differing malignant potential. A cell model of tumour development and progression comprising 2 non-tumorigenic adenoma lines and 4 carcinoma lines of increasing tumorigenicity was chosen. A gradual reduction in cellular differentiation and an accumulation of genetic alterations from adenoma to carcinoma characterized the selected cell lines. One-dimensional and 2-dimensional MRS showed that reduced differentiation in the cell model correlated with an increase in the levels of lipid, metabolites, the glycosylation intermediate uridine diphospho-N-acetylglucosamine and cell-surface fucosylation. Mutations involving the K-ras, APC and DCC genes are present both in adenoma- and in carcinoma-derived lines in this model, but the first evidence of an abnormality in the p53 gene was concomitant with the cells' ability to grow as a tumour in athymic nude mice. This genetic change coincided with the detection, by MRS, of UDP-hexose (ribose moiety, 2D MRS cross peak between H2 at 4.38 ppm and HI at 5.99 ppm) and the appearance of an additional fucosyl resonance (cross peak between-CH3 at 1.41 and H5 at 4.30 ppm) in the least tumorigenic of the carcinoma cell lines. An increase in complexity of the fucosylation spectral pattern was observed with further cellular de-differentiation and increased tumorigenicity. Collectively these data support the existence of an adenoma-carcinoma sequence.
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PMID:Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy. 792 26

We report here the use of multiplex fluorescent polymerase chain reaction (PCR) for quantitative allele loss detection using microsatellites with 2-5 base pair repeat motifs. Allele loss of APC, DCC, p53 and RB1 in colorectal tumours has been reported previously using a variety of methods. However, not all workers used intragenic markers. We have used microsatellite polymorphisms which map within, or are closely linked to, these tumour-suppressor gene loci in order to determine whether these loci are indeed the targets for alteration in colorectal cancer. In addition, we have assayed two other tumour-suppressor genes, WT1 and NF1, to see whether they play a role in colorectal carcinogenesis. The putative metastasis-suppressor gene, NM23, was also investigated since there have been conflicting reports about its involvement in colorectal carcinogenesis. Allele loss was detected at the DCC (29%), p53 (66%), RB1 (50%) and NF1 (14%) loci and in the APC/MCC region (50%), but not at the WT1 or NM23 loci. These rapid, and mostly gene-specific, fluorescent multiplex PCR assays for allele loss detection could be modified to devise a single molecular diagnostic test for the important lesions in colorectal cancer.
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PMID:Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. 794 85


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