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)

During the past few years molecular genetics has been providing answers concerning the mechanisms that are involved in the pathogenesis of human malignancies. Essentially two different mechanisms are involved. One results in the activation of cellular protooncogenes. This activation can occur by activation of transcription, mutation, or gene fusion. Chromosomal translocations and inversions in malignant cells have provided very powerful tools to identify and characterize genes involved in malignant transformation and to probes specific for breakpoint cluster regions are being used extensively for the diagnosis, prognosis, and clinical monitoring of hematopoietic malignancies. The other mechanism results in loss of function of cancer suppressor genes or antioncogenes. Loss of heterozygosity at specific sites of the human genome has provided the means to identify, by the molecular genetic approach, genes the function of which is eliminated or suppressed in human cancers. During the last few years a number of such genes, such as Rb and p53, have been identified and characterized. By this approach a potential candidate involved in the 3p deletion characteristic of lung cancer has been identified. Interestingly, this gene codes for a protein tyrosine phosphatase (14). If this gene should turn out to be involved in the pathogenesis of lung and kidney tumors, it will indicate that transmembrane protein tyrosine phosphatase may represent a class of tumor suppressors.
Cancer Res 1991 Sep 15
PMID:Genetic approaches to the study of the molecular basis of human cancer. 165 9

The papillomaviruses associated with human anogenital carcinomas encode two transforming genes, E6 and E7. The oncoprotein products of these two genes complex with the tumor suppressor gene products p53 and pRB, respectively. The loss of the normal function of these tumor suppressor gene products, either as a consequence of their association with E6 and E7 or by mutation, appears to be a common event in human cervical carcinogenesis.
Cancer Res 1991 Sep 15
PMID:Role of the human papillomaviruses in human cancer. 165 10

Human arterial smooth muscle cells transfected with the plasmid pSV3-neo, which contains the SV40 virus early region and the neor gene, developed colonies of morphologically transformed cells. Five cell strains were initiated from these colonies and could be subcultivated for up to 9 months before entering a stage of crisis that ended their life span. Deoxyribonucleic acid (DNA) molecules containing viral sequences were found free and integrated in the transformed cells. The intranuclear SV40 large T antigen and the p53 cellular protein were expressed in the transformed cells. Most of the transformed cells were spindle shaped but some were large and multinucleated. The modal chromosome numbers were in the triploid range, and aberrations, particularly dicentrics, were common. The transcripts for smooth muscle actins were significantly reduced and there were less alpha-actin filaments detected by immunofluorescence. Cytochemical staining disclosed a large accumulation of lipid droplets in the transformed cells incubated with rabbit hypercholesterolemic beta-very-low-density lipoprotein. Chemical analysis showed that cholesteryl esters were significantly elevated in these cells. Phenotypic changes induced in human vascular smooth muscle cells by SV40 early genes are similar to those found in smooth muscle cells from atherosclerotic lesions and may indicate common pathogenetic mechanisms.
Am J Pathol 1991 Sep
PMID:Characterization of human vascular smooth muscle cells transformed by the early genetic region of SV40 virus. 165 20

Infection of normal human diploid fibroblasts (HF) with the DNA tumor virus simian virus 40 (SV) leads to an extension of lifespan and concomitant increase in the levels of the viral large tumor antigen (T antigen) and the cellular protein p53. The intracellular localization of T antigen and p53 was mostly nuclear in both SVpre-crisis and SVpost-crisis cells, however certain population doubling (PD) of the SVpre-crisis cells exhibited some cytoplasmic staining. The DNA content of SVpre-crisis cells shifted to tetraploidy and the SVpost-crisis cells were near-tetraploid. Quantitation of T antigen and p53 in single cells by flow cytometry demonstrated that for all antibodies tested the levels of T antigen were higher in the SVpre-crisis HF than in the SVpost-crisis. The quantity of p53 increased with increasing age of SVpre-crisis HF, and the levels of p53 were higher in the SVpost-crisis HF populations. Immunoprecipitation of p53, T antigen and complexes demonstrated that all p53 was bound to T antigen in SVpre-crisis HF and SVpost-crisis HF. The SVpre-crisis HF cells showed that 33% of all T antigen was bound to p53, while 67% was free, and the SVpost-crisis HF exhibited 50% free T antigen and 50% bound to p53. The half-life of p53 was similar in all SVpre-crisis HF; however, the half-life was 2-3 times greater in SVpost-crisis HF than in SVpre-crisis HF. These results suggest that the interaction of DNA (ploidy), T antigen, p53 and complexes may be involved in formation of a stable SV40-transformed human cell line.
Oncogene 1991 Sep
PMID:T antigen and p53 in pre- and post-crisis simian virus 40-transformed human cell lines. 165 67

Malignant gliomas and medulloblastomas which are the most common primary malignant brain tumours of adult and children, respectively, resemble other neurogenic tumours as they frequently contain gene amplification and show non-random loss of specific chromosomal regions. In gliomas the gene which is most often amplified, is the epidermal growth factor receptor gene. In many cases the gene is rearranged as well, producing abnormally small epidermal growth factor receptor proteins. More than 80% of tumours have lost chromosome 10 and losses of 9p13, 17p and 22 occur in subgroups of cases. 17p loss is associated with point mutations of the p53 gene, but the relevant genes in the other chromosomal regions remain to be identified. For medulloblastoma the most frequent chromosomal abnormality is i(17q). Whether or not p53 gene mutations are the targets of 17p losses in these tumours remains to be determined. Approximately 5% of medulloblastoma biopsies contain gene amplification, although the incidence in medulloblastoma cell lines is more than 80%. c-myc is the gene which is most frequently amplified in this tumour type. The relationship of these various molecular genetic abnormalities to the biology of the tumours and the course of the patients remains largely unexplored.
Brain Pathol 1990 Sep
PMID:Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma. 166 88

We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited.
Proc Natl Acad Sci U S A 1991 Sep 01
PMID:Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. 167 37

Osteosarcoma tumorigenesis is consistent with a model by which tumorigenesis results if both alleles at the retinoblastoma susceptibility locus (RBI) are altered. Additional genetic evidence strongly suggests that another obligate event in osteosarcoma tumorigenesis is the homozygous alteration of another gene, p53. Both the RB1 gene and p53 have been proposed to act as tumor-suppressor genes, suggesting that, in this instance, tumorigenesis is the result of the loss of gene function of these two genes, rather than a gain of function.
Clin Orthop Relat Res 1991 Sep
PMID:Molecular genetic considerations in osteosarcoma. 167 82

A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p less than 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value.
Lancet 1991 Sep 21
PMID:Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. 167 68

We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (1/5). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 or higher levels of mutant p53 in comparison with more normal cells.
J Histochem Cytochem 1991 Sep
PMID:Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors. 168 Aug 97

Astrocytomas, including the most malignant form, glioblastoma multiforme, are the most frequent and deadly primary tumors of the human nervous system. Recent molecular genetic analyses of astrocytomas have demonstrated frequent chromosome 17 deletions involving the telomeric region of the short arm (17p12-pter). This region contains a candidate tumor suppressor gene, TP53, which has recently been implicated in the etiology of a broad array of human cancers. To study the possible role of TP53 in astrocytoma development, 24 randomly chosen human astrocytic tumors were examined for genomic TP53 sequence aberrations using primer-directed DNA amplification in conjunction with direct sequencing. Five of the 11 grade III astrocytomas (glioblastoma multiforme), but only one of seven grade II astrocytomas (anaplastic astrocytoma) and none of either the grade I astrocytomas or oligodendrogliomas demonstrated distinct point mutations involving the TP53 gene. These data suggest that TP53 mutations may play a role in astrocytoma development and are predominantly associated with higher grade tumors.
Genes Chromosomes Cancer 1991 Sep
PMID:TP53 gene mutations and 17p deletions in human astrocytomas. 168 25


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