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)

Granulomas occurring in sarcoidosis with lung involvement are mostly located in the paravasal interstitium, pleura, bronchial mucosa and stroma. The phases and the activity of the disease process are characterised by different patterns from multicellular epitheloidcellular granulomas to marked hyalinisations and scarifications. For the purpose of histochemical characterisation of the composition of the cells and matrix of pulmonary granulomas in open and transbronchial lung biopsies of 15 patients suffering from sarcoidosis in different clinical stages, antibodies were employed against macrophages, neutrophil elastase, collagen types I and III, fibronectin, laminin, PCNA and against the tumour suppressor gene product P53. Identification was subsequently performed either by means of indirect immunofluorescence or the PAP technique. Multicellular granulomas showed, especially centrally, a specific fluorescence for macrophages involving also giant cells, whereas antibodies against neutrophil elastase could be mainly identified peripherally. PCNA and P53 protein were identified in the cytoplasm and partly also in the nuclei of giant cells. Collagen types I and III were mainly expressed pericentrally. Fibronectin was found in numerous multicellular epitheloid cellular granulomas not only in the peripheral collagen network but also centripetally oriented. The scarifying granulomas showed initially increased centripetal deposition of fibronectin followed by an addition of collagen types I and III. Laminin was always present in very small quantities only. The results obtained demonstrate a variable expression of matrix structures in sarcoidosis, dependent on the developmental stages of pulmonary granulomas, this expression being capable of control to some extent with the proportions of epitheloid cells, lymphocytes and macrophages that are present. Tumour suppressor gene p53 positive macrophage giant cells and adhesion molecules such as fibronectin participate in granuloma production to a varying extent.
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PMID:[Characterization of structural and cellular components in pulmonary sarcoidosis granuloma]. 868 5

The tumour suppressor protein p53 enhances the genetic stability of the cell and plays a critical role in tumour suppression. Equine p53 was analysed by sequencing exons 5 to 9, a region which includes most known mutations and all the mutational hotspots in the species that have been investigated. The fragment was amplified, cloned and sequenced from genomic and complementary DNA. A comparison of the predicted amino acid sequences between the horse and other species resulted in identities between 66 per cent with the clawed frog and 92 per cent with the cat. Using the single strand conformation polymorphism technique, exons 5 to 8 amplified from sarcoid tissue and peripheral leucocytes of 28 sarcoid-affected and 11 healthy horses were screened for mutations. No mutations were identified, suggesting that the frequency of p53 mutations in equine sarcoid might be low. However, the high incidence of bovine papillomavirus (BPV) infection in equine sarcoid may indicate the functional inactivation of p53 by BPV-encoded E6 protein.
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PMID:Tumour suppressor gene p53 in the horse: identification, cloning, sequencing and a possible role in the pathogenesis of equine sarcoid. 888 Sep 79

Genetic and epigenetic alterations in the equine sarcoid, a locally invasive skin tumour of equids, are still poorly characterized. Numerous studies have provided reliable evidence for the relationship between the development of cancer and the loss of function of a number of tumour suppressor genes. In the present study, we assessed methylation levels in the promoter region of SFN, S100A14 and POU2F3 genes in sarcoid samples to clarify whether DNA methylation may be associated with previously identified changes in the expression level of these genes during the course of tumour progression. Using bisulfite sequencing and clone sequencing, we detected that lesional samples had a significantly higher rate of DNA methylation in the analyzed S100A14A region than the corresponding normal skin tissue. A frequent methylation of the SFN and POU2F3 promoter sequences were observed in both the tumour samples and the control skin tissues. Further studies are needed to evaluate the role of aberrant methylation in sarcoid progression and to understand the mechanisms involved in reduced expression of SFN, S100A14 and POU2F3 genes in the lesional tissues.
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PMID:DNA methylation patterns of the S100A14, POU2F3 and SFN genes in equine sarcoid tissues. 3038 43