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)

Acute leukaemias are characterized by nonrandom chromosomal aberrations which are often strictly related to the inactivation of tumour suppressor genes (TSGs). Alterations at the short arm of chromosome 9 have been reported in a remarkable percentage of acute lymphoblastic leukaemias (ALL) and have been suggested to cause the loss of activity of the putative TSG, p16INK4A (MTS1/CDKN2) gene. In order to evaluate the correlation between this gene inactivation and visible cytogenetic abnormalities, we have investigated p16INK4A homozygous gene deletions in 10 paediatric acute leukaemias of different cell lineages which demonstrated karyotype aberrations involving chromosome 9. Moreover, the dimension of the genetic alteration was evaluated by studying the loss of heterozygosity of two highly polymorphic markers of chromosome 9p, namely alpha-interferon (IFNA) and D9S104, and the deletion of 5'-methylthioadenosine phosphorylase (MTAPase) gene. Finally, the deletion of a gene belonging to p16INK4A family, the p18 gene, was analysed in these acute leukaemias. Our results demonstrated that: (1) the biallelic loss of p16INK4A gene is strictly related to a specific immunophenotype, namely ALL of T-cell lineage; (ii) no significant correlation exists between alterations at chromosome 9p level and the homozygous deletions of p16INK4A gene; and (iii) p18 gene was not deleted in the examined cases. These findings suggest a possible correlation between the T-lymphocyte phenotype and the expression of p16INK4A gene. Moreover, the absence of MTAPase activity seems to be a valuable marker of p16INK4A gene inactivation, thus indicating that the deleted chromosomal area on 9p21 very frequently involves the MTAPase gene.
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PMID:P16INK4A gene homozygous deletions in human acute leukaemias with alterations of chromosome 9. 865 84

The methylthioadenosine phosphorylase (MTAP) gene is localized in the chromosomal region 9p21. Here, frequently homozygous deletions occur in several kinds of cancer associated with the loss of tumour suppressor genes as p16 and p15. The aim of this study was to analyse MTAP expression in hepatocellular carcinoma (HCC) and to get an insight into the regulation and functional role of MTAP in hepatocancerogenesis. Compared with primary human hepatocytes MTAP expression was markedly downregulated in three different HCC cell lines as determined by real-time PCR and western blotting. This was not due to genomic losses or mutations but to promoter-hypermethylation. Reduced MTAP-expression was confirmed in vivo in HCC compared with non-cancerous liver tissue on both mRNA and protein levels. To study the functional relevance of the downregulated MTAP expression in HCC, MTAP expression was re-induced in HCC cell lines by stable transfection. In these MTAP re-expressing cell clones the invasive potential was strongly reduced, whereas no effects on cell proliferation were observed in comparison with mock transfected cell clones. Furthermore, in MTAP re-expressing cells interferon (IFN)-alpha and IFN-gamma induced a significantly stronger inhibition of cell proliferation than in mock transfected cells. In conclusion, our results suggest a functional role of MTAP inactivation in HCC development and invasiveness. Furthermore, in the light of a recent report revealing an association between MTAP activity and IFN sensitivity, our findings may have clinical significance for therapeutic strategies.
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PMID:Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma. 1608 15

The methylthioadenosine phosphorylase (MTAP) gene is a tumour suppressor gene, located on chromosome 9p21, 100 kb telomeric of the p15 and p16 genes, which are often deleted in tumor cells. The role of MTAP protein expression in the genesis of cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity (AI/LOH) in cutaneous SCCs using AI/LOH markers flanking the p15, p16, and MTAP genes and demonstrated reduction in p15 and p16 protein expression in comparison to normal human skin. The present study is a continuation to our previous studies, aimed at determining possible roles played by MTAP protein expression in the genesis of cutaneous SCC. The expression of MTAP protein was detected using immunohistochemical approach in 109 micro array cutaneous SCC and 20 normal human skin tissue samples. The expression of MTAP was not significantly different in the cutaneous SCC cases as compared with normal human skin. This may indicate that MTAP protein expression does not contribute to the genesis of cutaneous SCC.
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PMID:Methylthioadenosine phosphorylase expression in cutaneous squamous cell carcinoma. 1871 77

It has recently been shown that there are highly significant associations for common single nucleotide polymorphisms (SNPs) near the CDKN2B-AS1 gene region at the 9p21 locus with primary open angle glaucoma (POAG), a leading cause of irreversible blindness. This gene region houses the CDKN2B/p15(INK4B) , CDKN2A/p16(INK4A) and p14ARF (rat equivalent, p19(ARF) ) tumour suppressor genes and is adjacent to the S-methyl-5'-thioadenosine phosphorylase (MTAP) gene. In order to understand the ocular function of these genes and, therefore, how they may be involved in the pathogenesis of POAG, we studied the distribution patterns of each of their products within human and rat ocular tissues. MTAP mRNA was detected in the rat retina and optic nerve and its protein product was localised to the corneal epithelium, trabecular meshwork and retinal glial cells in both human and rat eyes. There was a very low level of p16(INK4A) mRNA present within the rat retina and slightly more in the optic nerve, although no protein product could be detected in either rat or human eyes with any of the antibodies tested. P19(ARF) mRNA was likewise only present at very low levels in rat retina and slightly higher levels in the optic nerve. However, no unambiguous evidence was found to indicate expression of specific P19(ARF)/p14(ARF) proteins in either rat or human eyes, respectively. In contrast, p15(INK4B) mRNA was detected in much higher amounts in both retina and optic nerve compared with the other genes under analysis. Moreover, p15(INK4B) protein was clearly localised to the retinal inner nuclear and ganglion cell layers and the corneal epithelium and trabecular meshwork in rat and human eyes. The presented data provide the basis for future studies that can explore the roles that these gene products may play in the pathogenesis of glaucoma and other models of optic nerve damage.
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PMID:Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region. 2406 79