Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exon 8 of tumour suppressor gene p53 was sequenced in domestic dogs. Ten nucleotide differences were revealed in a comparison with the feline sequence. A mutation ACT-->TCT (threonine-->serine) in codon 284 was detected in a papilloma of the oral mucosa.
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PMID:Sequence of an exon of the canine p53 gene--mutation in a papilloma. 754 37

Overexpression of the p53 tumour suppressor gene is one of the most common abnormalities in primary human cancers and appears to be a result of point mutation within a highly conserved region of the gene with subsequent encoding for a mutant, more stable protein. In the study, 71 surgically resected hepatocellular carcinomas (HCC) were examined to study the expression of the p53 gene, its relation with clinicopathological parameters and its prognostic significance. Using immunohistochemical detection for mutant p53 protein with monoclonal antibody PAb1801, p53 overexpression was found in 22 tumours (31%) but in none of the non-tumorous liver specimens. Overexpression of p53 was more frequent in tumours with poor cellular differentiation (P = 0.01), in tumours > 5 cm in diameter (P = 0.05), and in those with giant cells present (P = 0.03) and, less significantly, of massive type of Eggel's classification (P = 0.06). It did not have any significant correlation with hepatitis B or C status, background liver disease or serum alpha-fetoprotein levels, nor was it related to tumour invasiveness (venous permeation, direct liver invasion and tumour microsatellite formation). In addition, the presence of p53 mutant protein did not influence tumour recurrence or patients' survival rates. The data suggested that p53 mutation in HCC was associated with a later stage of oncogenesis. However, it was not apparently related to tumour invasiveness/aggressiveness and prognosis.
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PMID:Overexpression of p53 in hepatocellular carcinomas: a clinicopathological and prognostic correlation. 754 99

The results of conventional treatments for lung cancer remain poor and long-term survival rates have changed little over the last 10 years. In the same period of time there has been an explosion in the knowledge on the processes of cellular transformation, tumour progression, invasion and metastasis. The major categories of biological events implicated in non-small cell lung cancer include growth factor receptors expression (epidermal growth receptor, p185c-neu), autocrine growth factor production (transforming growth factor alpha), dominant oncogenes activation (ras genes) and deletion of tumour suppressor genes (p53 gene, retinoblastoma gene) and these are some of the abnormalities associated with specific histological types and with poor prognosis. Additional prognostic information can be obtained from the evaluation of the ploidy and proliferative activity of the tumours, carbohydrate antigens expression, presence of neuroendocrine differentiation and the evaluation of markers of the sequential steps involved in the process of tumour dissemination.
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PMID:Biological prognostic factors in non-small cell lung cancer. 755 21

Loss of function of one or both of the two tumour suppressor genes p53 and RB-1 has been recognised as an important step in the development of a variety of human neoplasias for some time. By virtue of the ability to manipulate the genome of murine embryonic stem cells in culture, it has become possible to generate strains of mice which bear inactivations of the murine counterparts of these genes. This article attempts to bring together some of the many results obtained from these murine strains which are shedding light both on the normal role played by both of these genes and the consequences of their dysfunction. Surprisingly neither gene product is revealed to have an indispensable role at the level of the single cell. Hence, even though the Rb-1 gene product clearly has an important role in cell cycle regulation animals constitutively deficient in this gene develop relatively normally for the first 10 days of embryogenesis. It is only at and beyond this stage of development that a requirement for Rb-1 becomes clear, in the regulation of certain cell populations through control of both proliferation and apoptosis. That loss of function of Rb-1 is associated with tumorigenesis is confirmed by the development of tumours of the pituitary gland within heterozygotes. The retinas of these animals, the target organ for tumorigenesis in human RB-1 heterozygotes, remain unaffected. The majority of mice homozygous for an inactivating p53 mutation survive to birth, but then rapidly succumb to tumorigenesis. Heterozygotes also develop tumours, but with a delayed time course and altered spectrum. Analysis of several tissue types from the mutant animals has shown p53 to be crucial for the normal induction of apoptosis following DNA damage, and it is thought that failure of this process is a key predisposing step towards tumorigenesis within the mutant animals. Finally, studies on these and other transgenic strains have revealed interactions between pathways governed by these two genes. For example, the fate of Rb-1 deficient cells has been shown, in some tissues at least, to be dependent upon the functional status of p53.
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PMID:Murine models of neoplasia: functional analysis of the tumour suppressor genes Rb-1 and p53. 755 30

One of the most commonly detected abnormalities in human cancer is mutation of the p53 tumour suppressor gene. Intrinsic to the function of p53 is its ability to induce apoptotic cell death and to cause cell cycle arrest. Moreover, p53 plays an important role in controlling the cellular response to DNA damaging agents such as ionizing radiation and cancer chemotherapeutic drugs. Loss of p53 function causes increased resistance to radiation and chemotherapeutic agents, and there is increasing evidence that p53 mutational status is an important determinant of clinical outcome in cancer. This review will focus on recent data describing the biochemistry of p53 function, its role in mediating apoptosis and cell cycle arrest and in the control of tumour growth and death.
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PMID:Apoptosis, cancer and the p53 tumour suppressor gene. 755 31

When growth-arrested mouse fibroblasts re-entered the cell-cycle, the rise in tumour suppressor p53 mRNA level markedly preceded the rise in expression of the p53 protein. Furthermore, gamma-irradiation of such cells led to a rapid increase in p53 protein biosynthesis even in the presence of the transcription inhibitor actinomycin D. Both findings strongly suggest that p53 biosynthesis in these cells is regulated at the translational level. We present evidence for an autoregulatory control of p53 expression by a negative feed-back loop: p53 mRNA has a predicted tendency to form a stable stem-loop structure that involves the 5'-untranslated region (5'-UTR) plus some 280 nucleotides of the coding sequence. p53 binds tightly to the 5'-UTR region and inhibits the translation of its own mRNA, most likely mediated by the p53-intrinsic RNA re-annealing activity. The inhibition of p53 biosynthesis requires wild-type p53, as it is not observed with MethA mutant p53, p53-catalysed translational inhibition is selective; it might be restricted to p53 mRNA and a few other mRNAs that are able to form extensive stem-loop structures. Release from negative feed-back regulation of p53 biosynthesis, e.g. after damage-induced nuclear transport of p53, might provide a means for rapidly increasing p53 protein levels when p53 is required to act as a cell-cycle checkpoint determinant after DNA damage.
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PMID:Negative feedback regulation of wild-type p53 biosynthesis. 755 87

The treatment and prognosis of patients with cerebral astrocytic tumours are currently guided by histopathological classification. This study evaluates immunohistochemistry using Ki-67, an antibody to a nuclear protein expressed in proliferating cells, and DO-7, an antibody to the product of the tumour suppressor gene p53, as prognostic indicators for these tumours. Immunohistochemistry with Ki-67 has been correlated with the behaviour of many different tumours, but its value as a prognostic indicator in astrocytic tumours is diminished by the conflicting results of previous studies. Immunohistochemistry with antibodies to the p53 protein has been used as a prognostic indicator in melanomas and some carcinomas, but the relation between prognosis and accumulation of this protein in astrocytic tumours has not been clarified. We have tested the hypothesis that survival is correlated with Ki-67 immunolabelling indices (LIs) and patterns of p53 immunolabelling in the cerebral astrocytic tumours of a large cohort of patients (n = 123) for whom clinical indices were well documented. Astrocytic tumours were divided into three histological types: fibrillary astrocytoma (n = 24), anaplastic astrocytoma (n = 31), and glioblastoma (n = 68). Histological type and patient age were independent predictors of survival. Median Ki-67 LIs differed significantly (P < 0.0001) between the types of astrocytic tumour, and tumours with a Ki-67 LI < 2% had a significantly (P < 0.0001) better prognosis. Ki-67 LI as a continuous variable carried a significant (P = 0.0043) unadjusted hazard to survival which was lost when adjusted for other variables, notably histological type. By contrast, no relation was found between survival and three categories of p53 labeling (p53-negative, p53 LI < 40%, and p53 LI > 60%). The results indicate that, whereas Ki-67 immunohistochemistry predicts survival in patients with astrocytic tumours, conventional histological appraisal remains the best guide to prognosis, and immunohistochemistry for p53 has no value in the assessment of these tumours.
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PMID:Prognostic indicators in a range of astrocytic tumours: an immunohistochemical study with Ki-67 and p53 antibodies. 756 22

The loss of specific chromosomal loci in cancers is indicative that the region contains a tumour suppressor gene. Allelic loss of chromosome 17p has been shown to occur in a wide variety of cancers such as lung, breast, colon, ovary and brain and, until recently, the gene believed to be involved was the p53 tumour suppressor gene. However, more recent studies have shown that the area deleted in some of these tumours does not include the structural gene for p53. For this reason it has been proposed that a tumour suppressor gene lying distal to p53 on chromosome 17p is the gene deleted in these cancers. As chromosome 17p has been shown to be deleted in approximately 75% of colorectal cancers, we set out to determine whether the target gene of these deletions was the structural gene for p53. Allelic loss was assessed by using restriction fragment length polymorphisms in 52 tumours. Deletions distal to p53 on chromosome 17p were assessed using the probe YNZ22.1 and allelic loss of p53 was assessed using probe pR4-2, a cDNA probe specific for the p53 gene. Out of the 21 tumours informative for both probes, 3 cases showed no allelic deletion of the chromosome 17p, 2 cases showed allelic deletion not encompassing the p53 gene and 16 cases (89%) showed allelic deletion including the p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allelic loss of the p53 gene in colorectal cancer. 757 22

The human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild-type p53, as it is not observed in cells lacking functionally wild-type protein, and at least some component of S phase and G2/M arrests is also thought to be p53-dependent. p53 functions as a transcription factor which binds specific DNA sequences, and recently major downstream targets have been identified, including p21Cip1, an inhibitor of the cell cycle kinases that also blocks the replicative but not the repair function of DNA polymerase delta auxiliary factor, PCNA. Current interest focuses on developing novel cancer therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell cycle.
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PMID:Tumour suppressors, kinases and clamps: how p53 regulates the cell cycle in response to DNA damage. 757 91

Numerous clinical, epidemiological and molecular findings link some types of Human Papillomaviruses (HPV) with cancer of the genital tract. They share a common pathway of transformation with a number of DNA tumour viruses, such as Adenovirus and SV40. Although all these viruses are termed 'DNA tumour viruses' and have similar in vitro transforming activities, Human Papillomavirus is the only one so far clearly involved in human cancer. Extensive studies on HPV E6 and E7 proteins have demonstrated their involvement in malignant transformation. E6 and E7 bind the products of tumour suppressor genes, p53 and Rb1, respectively, modifying or inactivating their normal functions. The Rb1 and p53 genes are deleted or mutated in several cancers and both proteins regulate the transcription of genes involved in cell cycle progression control. The E6/p53 and E7/Rb1 interactions result in a deregulation of the cell cycle with loss of control of crucial cellular events, such as DNA replication, DNA repair and apoptosis.
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PMID:Human papillomavirus E6 and E7: proteins which deregulate the cell cycle. 757 92


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