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)

The state of p53 tumour suppressor and the frequency of high-risk human papillomavirus (HPV) infections were studied in nine human oral cancer cell lines. Three cancer cell lines (SCC-4, Tu-177 and FaDu) had similar amounts of p53 transcripts to normal cells, but contained significantly higher levels of p53 protein than the normal control cells. Sequencing highly conserved open reading frames of the p53 gene of these cancer cells showed point mutations in the SCC-4 and Tu-177 cell lines, a base transition from CCC to TCC occurred at codon 151; and in the line FaDu, a mutation of CGG to CTG occurred at codon 248. The HEp-2 and 1483 cancer lines contained significantly lower levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations, but northern analysis revealed that these cell lines expressed HPV-18 E6/E7 messages. Four cell lines (SCC-9, SCC-15, SCC-25, and Tu-139) expressed negligible amounts of p53 transcripts compared to the normal counterpart and undetectable levels of p53 protein. These cell lines contained mutations in the highly conserved open reading frames of the p53 gene as follows: the SCC-9 had a deletion of 32 base pairs between codons 274 and 285; the line SCC-15 had an insertion of five base pairs between codons 224 and 225; the line SCC-25 had a deletion of two base pairs in codon 209; and the Tu-139 line had a deletion of 46 base pairs between codons 171 and 186.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur J Cancer B Oral Oncol 1994 Sep
PMID:Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines. 770 4

The interferon-inducible protein kinase PKR interacts with a number of small viral RNA species, including adenovirus VAI RNA and the Epstein-Barr virus-encoded RNA EBER-1. These RNAs bind to PKR and protect protein synthesis from inhibition by double-stranded RNA in the reticulocyte lysate system. Using a peptide phosphorylation assay we show here that EBER-1, like VAI, directly inhibits the activation of purified PKR. A second Epstein-Barr virus RNA, EBER-2, also regulates PKR. EBER-1, EBER-2 and VAI RNA exhibit mutually competitive binding to the native or recombinant enzyme, as assessed by U.V. crosslinking experiments and filter binding assays. The affinities of all three RNAs for PKR in vitro are similar (Kd = ca. 0.3 nM). Since this protein kinase has been proposed to exert a tumour suppressor function in vivo, the ability of EBER-1 to inhibit its activation suggests a role for this small RNA in cell transformation by Epstein-Barr virus.
Nucleic Acids Res 1993 Sep 25
PMID:Comparative analysis of the regulation of the interferon-inducible protein kinase PKR by Epstein-Barr virus RNAs EBER-1 and EBER-2 and adenovirus VAI RNA. 790 35

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.
Br J Dermatol 1994 Sep
PMID:Immunohistochemical localization of lysyl oxidase in normal human skin. 791 5

The genes coding for two metalloproteases, EcH-I and EcH-II, have been cloned from an Echis pyramidum leakeyi venom gland cDNA library. The cDNA sequences predict two zymogen molecules with strong amino acid sequence similarity and the same domain structure present in other members of the viper metalloprotease/disintegrin gene family. EcH-I and EcH-II contain pro-protein, enzyme and disintegrin domains. Analysis of the cDNAs coding for EcH-I, EcH-II, jararhagin, trigramin and Ht-e reveals a strong similarity, particularly in the untranslated regions and regions coding for the pro-peptide. Comparison of EcH-I and EcH-II with venom metalloproteases, mammalian matrix-degrading metalloproteases, sperm proteins, and a potential tumour suppressor gene highlights the presence of a number of motifs with potential functional significance.
Eur J Biochem 1994 Sep 01
PMID:Cloning of metalloprotease genes in the carpet viper (Echis pyramidum leakeyi). Further members of the metalloprotease/disintegrin gene family. 792 63

Mutations in oncogenes and tumour suppressor genes may have an important oncogenic role. Although flat type tumours have been frequently detected in recent years, ras and p53 expressions have not been studied in these tumours. Using a monoclonal and polyclonal antibody to the ras p21 and p53 product, paraffin wax embedded sections of 98 colorectal tumours (43 cases of the flat type colorectal tumour and 55 cases of polypoid type tumour) were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination. Positive staining rate of ras p21 for the flat type was 0%; for the polypoid type, it was 60% in cancer with submucosal invasion, 82% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The positive staining rate of p53 for the flat type was 50% in submucosal cancer, 9% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. For the polypoid type, it was 40% in submucosal cancer, 12% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The intermediate staining rate of p53 in the polypoid type was 20% in submucosal cancer and 41% in adenoma with high grade dysplasia. It was seen that p53 was commonly expressed in both flat and polypoid lesions, p21 was not expressed in flat lesions, whereas it was commonly expressed in polypoid neoplasms. In the flat type cancer, a genetic change different from that of the polypoid type cancer is suggested.
Gut 1994 Sep
PMID:Comparative clinicopathological and immunohistochemical study of ras and p53 in flat and polypoid type colorectal tumours. 795 33

Mutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic lesions, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.
J Pathol 1994 Sep
PMID:Human non-small cell lung cancer: p53 protein accumulation is an early event and persists during metastatic progression. 767 94

This article reviews the contribution of modern investigative techniques to the diagnosis of cutaneous lymphoproliferative diseases. Special attention is given to the significance of immunoglobulin and T-cell receptor rearrangements; as detected by Southern blotting and/or the polymerase chain reaction. Additional topics discussed include immunohistochemistry, cytogenetics, onco- and tumour suppressor genes and in-situ hybridization. It is recommended that the results of these techniques are interpreted in the form of a multifaceted diagnostic profile.
Semin Dermatol 1994 Sep
PMID:Review of investigative diagnostic techniques for cutaneous lymphoma. 798 84

Mice constitutively lacking alleles of the p53 tumour suppressor gene spontaneously develop lymphomas and sarcomas. We report here that a single dose of 4 Gy radiation dramatically decreases the latency for tumour development in p53 heterozygous mice. The pattern of genetic alterations at the remaining wild type allele in these tumours differs substantially from spontaneous tumours from similar mice indicating that p53 itself may have been a target for radiation-induced alterations. Lower dose irradiation (1 Gy) of preweanling p53 null mice also significantly decreases tumour latency, suggesting that there are additional genetic targets involved in radiation-induced malignancy. Thus p53-deficient mice provide a sensitive model system for studies of the consequences of radiation exposure.
Nat Genet 1994 Sep
PMID:p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. 798 94

Abnormalities of the p53 tumour suppressor gene occur in many types of cancer including approximately 60% of colorectal carcinomas. This study investigates in 47 colorectal carcinomas the relationship between stabilised p53 protein detected by immunocytochemistry (ICC), and p53 mutation. 27 cases stained positively with the antibody PAb1801. Sequencing of exons 5-8 revealed 19 mutations in 18 of these cases (one tumour contained two different mutations). A rapid, non-radioactive method was developed to screen for mutations in this region of the gene involving Single Strand Conformational Polymorphism analysis (SSCP) and a MspI restriction digestion. This screen detected 17/19 (89%) of the sequenced mutations, and a further four mutations in 20 PAb1801 negative cases that were confirmed by sequencing. Reproducibility of ICC in detecting stabilised protein was assessed by restaining the 47 cases with the antibody DO7 after pre-treatment to optimise detection. Fewer cases were negative with DO7 although overall concordance with PAb1801 was good. A substantial proportion of carcinomas with stabilised p53 as detected by ICC do not contain mutations in exons 5-8, whilst some mutations (the majority in exon 6) are not associated with stabilisation.
Oncogene 1994 Sep
PMID:A study of stabilisation of p53 protein versus point mutation in colorectal carcinoma. 805 40

The tumour suppressor p53 specifically interferes with the onset of S phase. The mechanism of the growth suppression action of the protein is unclear, though recent evidence points to transcriptional activation and repression functions of the protein. A competing hypothesis suggests that p53 interacts with the DNA replication apparatus and directly interferes with DNA replication. The major evidence for this hypothesis is that p53 interacts with the simian virus 40 (SV40)-encoded protein T antigen and interferes with the ability of T antigen to unwind the SV40 origin of DNA replication, and recruit DNA polymerase alpha to the replication initiation complex. Here we report that p53 physically interacts with and inhibits the function of a cellular DNA replication factor, the single-stranded DNA-binding protein complex RPA.
Nature 1993 Sep 02
PMID:Inhibition of DNA replication factor RPA by p53. 836 31


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