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)

Several genetic alterations have been implicated in the development of malignant melanoma, but the expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes and their interactions in melanoma have not been completely clarified. We simultaneously examined the expression of p73, c-erbB-2, ras, p53, Mdm2, p27, DCC, hMLH-1, hMSH-2, bcl-2, Bax and NF-kappaB, by immunocytochemistry, in both primary and metastatic melanoma cell lines derived from melanoma patients. p73 was expressed in 7/8 cell lines, but stronger expressed in the metastatic cells than in the primary melanoma cells. c-erbB-2 was detected in all 8 cell lines and ras in 2/5 metastases. p53 was found in all the cell lines and Mdm2 in 1/8 of the cell lines. In the same patient, the intensity of p27 expression was decreased from the primary to the metastatic tumours. bcl-2 was expressed in all the cell lines. Bax was absent in 5/8 cell lines. In the same patient, Bax was weakly expressed in the primary tumour but lacking in the metastases. The data demonstrate that overexpression of p73, c-erbB-2, p53 and bcl-2, and loss of Mdm2 and Bax may interact and play important roles in the development and aggressiveness of human melanoma.
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PMID:Expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells. 1171 83

LT97, a permanent cell line consisting of epithelial cells with an early premalignant genotype was established from small colorectal polyps. LT97 cells have lost both alleles of the APC tumour suppressor gene. In addition, they carry a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are thus representative of early adenomas. They had to be passaged as multicellular aggregates indicating a dependency of survival on cell-cell contact and in accordance with their premalignant genotype were not capable of growth in soft agar. LT97 cells did express both the EGF-receptor and small amounts of TGF(alpha) establishing an autocrine growth or survival pathway. However, in spite of autocrine TGF(alpha) production, growth was strongly dependent on exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF-receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar indicating that TGF(alpha) activated survival pathways in the early adenoma cell.
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PMID:Cells obtained from colorectal microadenomas mirror early premalignant growth patterns in vitro. 1220 77

In vivo investigations on oncogenes and onco-suppressor genes may provide new findings on the potential carcinogenic effects of various cytostatic protocols inducing secondary tumours of the head and neck. Further surgeries are often necessary due to regional recurrence after the Cisplatin-supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol in the treatment of human head and neck tumours. Our earlier studies have illustrated the carcinogenic and mutagenic potential of Cisplatin. The effect of Cisplatin on the alteration of different onco- and suppressor genes has also been proven. Our present study aimed at investigating the early effects of the BVM and the CFu (Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour suppressor gene expressions in mice. Body weight equivalent amounts of cytostatics were administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes were examined. The protocols caused detectable changes. A "short-term" in vivo test, the 24-hour examination of gene expression, is suitable for detecting early effects of carcinogen exposure. The alterations of gene expression, caused by the Cisplatin-containing protocol, draw attention to the probable role of Cisplatin in the development of regional recurrence and to the possibility of prevention.
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PMID:Early effects of different cytostatic protocols for head and neck cancer on oncogene activation in animal experiments. 1498 32

Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer and is a common cancer type worldwide. Many aetiological factors have been related to HCC development, such as liver cirrhosis, hepatitis viruses and alcohol consumption. Inactivation of the p53 tumour suppressor gene is one of the most common abnormalities in many tumours, including HCC. p53 is of crucial importance for the regulation of the cell cycle and the maintenance of genomic integrity. In HCC, hepatitis B and C virus (HBV and HCV) effect carcinogenic pathways, independently leading to anomalies in p53 function. Several authors have reported that some HCV proteins, such as the core, NS5A and NS3 proteins, interact with p53 and prevent its correct function. The mechanisms of action of these HCV proteins in relation to p53 are not completely clear, but they might cause its cytoplasmic retention or accumulation in the perinuclear region where the protein is not functional. The identification of the interactions between p53 and HCV proteins is of great importance for therapeutic strategies aimed at reducing the chronicity and/or carcinogenicity of the virus.
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PMID:Hepatocellular carcinoma: molecular interactions between hepatitis C virus and p53 in hepatocarcinogenesis. 1498 3

The N-terminal 198 residues of NS3 (NS3-N) of Hepatitis C virus (HCV) subtype 1b obtained from 29 patients, as well as full-length NS3 (NS3-Full), were analysed for their subcellular localization, interaction with the tumour suppressor p53 and serine protease activity in the presence and absence of the viral cofactor NS4A. Based on the subcellular-localization patterns in the absence of NS4A, NS3-N sequences were classified into three groups, with each group exhibiting either dot-like, diffuse or a mixed type of localization. Chimeric NS3-Full sequences, each consisting of an individual NS3-N and a shared C-terminal sequence, showed the same localization patterns as those of the respective NS3-N. Site-directed mutagenesis experiments revealed that a single or a few amino acid substitutions at a particular position(s) of NS3-N altered the localization pattern. Interestingly, NS3 of the dot-like type, either NS3-N or NS3-Full, interacted with p53 more strongly than that of the diffuse type, in both the presence and the absence of NS4A. Moreover, NS3-N of the dot-like type suppressed trans-activating activity of p53 more strongly than that of the diffuse type. Serine protease activity did not differ significantly between the two types of NS3. In HCV RNA replicon-harbouring cells, physical interaction between NS3 and p53 was observed consistently and p53-mediated transcriptional activation was suppressed significantly compared with HCV RNA-negative control cells. Our results collectively suggest the possibility that NS3 plays an important role in the hepatocarcinogenesis of HCV by interacting differentially with p53 in an NS3 sequence-dependent manner.
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PMID:NS3 protein of Hepatitis C virus associates with the tumour suppressor p53 and inhibits its function in an NS3 sequence-dependent manner. 1669 Sep 37

Aims-To determine possible associations between p53 allelic deletion, c-Ki-ras mutational activation, immunohistochemical detection of p53 and ras proteins, various clinicopathological variables, and patient outcome in 168 Dukes' stage B colorectal carcinomas.Methods-Allelic deletion at the p53 tumour suppressor gene locus was detected using polymerase chain reaction (PCR) based loss of heterozygosity (LOH) assays. Overexpressed proteins were detected using the CM1 polyclonal antibody. A PCR based assay was used to detect the presence of activating mutations at codon 12 of c-Ki-ras. Immunostaining was carried out using a monoclonal antibody to p21(ras).Results-p53 LOH, CM1 immunostaining, c-Ki-ras mutational activation, and p21(ras) immunostaining were not predictive of survival by logrank analysis. Multivariate analysis using Cox regression did not predict survival in this group of tumours.Conclusions-Aberrations in ras and p53 are unlikely to play an important role in the subdivision of patients with Dukes' stage B colorectal carcinoma into more accurate prognostic strata. It is possible that later genetic events are more important in conferring a specific phenotype on the resultant Dukes' stage B tumour.
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PMID:ras and p53 in the prediction of survival in Dukes' stage B colorectal carcinoma. 1669 29

Disseminated neoplasia has been reported in mussels (Mytilus spp) from numerous locations worldwide. This condition is progressive and fatal and the aetiology is unknown. In vertebrates, oncogenes such as ras, and tumour suppressor genes such as p53, play important roles in carcinogenesis. We have cloned a Mytilus trossulus homologue of the vertebrate ras gene, which shows conserved sequence in regions of functional importance. Neoplastic hemolymph samples derived from M. trossulus have been investigated for the presence of ras gene mutations and changes in expression.
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PMID:The role of ras gene in the development of haemic neoplasia in Mytilus trossulus. 1669 73

Normal human thyroid follicular epithelial cells exhibit a very low proliferative rate which in vitro is dramatically increased by RAS oncogene activation, resulting in clones displaying a phenotype consistent with that of a ras-induced follicular adenoma in vivo. Eventual spontaneous cessation of growth of these clones is closely correlated with increasing expression of the tumour suppressor gene p16(INK4a), suggesting that p16 may limit clonal expansion in this tumour model. We therefore hypothesised that p16 expression would also increase in vivo in follicular adenomas, and further that escape from growth control in follicular cancers would be accompanied by loss of p16 expression. This was tested using tissue microarrays, representing multiple stages of thyroid tumourigenesis. Whereas the majority of normal thyroids showed no immunostaining, p16 protein was readily detectable in follicular adenomas. Unexpectedly, however, p16 expression was also observed in follicular and papillary carcinomas. Poorly differentiated (insular) carcinomas showed either very intense staining, or a complete loss of staining. We conclude that loss of p16 is not necessary for malignant transformation in thyroid follicular cells, but that it may form one of two or more events needed for progression to more aggressive forms of thyroid cancer.
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PMID:An immunohistochemical study of p16(INK4a) expression in multistep thyroid tumourigenesis. 1704 39

RASSF2 is a recently identified member of a class of novel tumour suppressor genes, all containing a ras-association domain. RASSF2 resides at 20p13, a region frequently lost in human cancers. In this report we investigated methylation status of the RASSF2 promoter CpG island in a series of breast, ovarian and non-small cell lung cancers (NSCLC). RASSF2 was frequently methylated in breast tumour cell lines (65%, 13/20) and in primary breast tumours (38%, 15/40). RASSF2 expression could be switched back on in methylated breast tumour cell lines after treatment with 5'-aza-2'deoxycytidine. RASSF2 was also frequently methylated in NSCLC tumours (44%, (22/50). The small number of corresponding normal breast and lung tissue DNA samples analysed were unmethylated. We also did not detect RASSF2 methylation in ovarian tumours (0/17). Furthermore no mutations were found in the coding region of RASSF2 in these ovarian tumours. We identified a highly conserved putative bipartite nuclear localization signal (NLS) and demonstrated that endogenous RASSF2 localized to the nucleus. Mutation of the putative NLS abolished the nuclear localization. RASSF2 suppressed breast tumour cell growth in vitro and in vivo, while the ability of NLS-mutant RASSF2 to suppress growth was much diminished. Hence we demonstrate that RASSF2 has a functional NLS that is important for its tumour suppressor gene function. Our data from this and a previous report indicate that RASSF2 is frequently methylated in colorectal, breast and NSCLC tumours. We have identified RASSF2 as a novel methylation marker for multiple malignancies and it has the potential to be developed into a valuable marker for screening several cancers in parallel using promoter hypermethylation profiles.
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PMID:Epigenetic regulation of the ras effector/tumour suppressor RASSF2 in breast and lung cancer. 1789 Nov 78

Archival formalin-fixed tissues from wild-caught adult blue sharks, Prionace glauca (L.), were used for immunocytochemical detection of proliferating cell nuclear antigen (PCNA), two oncoproteins from the oncogenes c-myc and pan-ras, and a protein product from the tumour suppressor gene p-53. All sharks were caught during summer months between 2000 and 2006 by recreational fishermen off the USA coast in the northwestern Atlantic. The sharks were necropsied on landing and selected organ samples were collected into elasmobranch formalin and processed for paraffin embedding and light microscopy. Paraffin-embedded sections from collected tissue were both stained with haematoxylin and eosin and processed by immunocytochemical techniques using antibodies raised against the PCNA, p-ras, c-myc and p-53 proteins. The lesions examined in this study included two well differentiated adenomatous gastric polyps, a testicular capsular mesothelioma, a gingival fibropapilloma with elements of ameloblastoma, three liver tumours, two pericardial fibropapillomas and six cases of proliferative serositis (pericarditis and peritonitis). Normal and hyperplastic tissues from blue sharks, and human neoplastic tissues served as negative and positive controls, respectively. We detected upregulation of PCNA in many neoplastic, one dysplastic and in some hyperplastic lesions, and positive p-ras and c-myc signals in some of the neoplastic lesions. None of the examined tissues showed positive p-53 signalling. This is the first literature report on immunocytochemical detection of molecular markers of cancer in sharks and in fish of the class Chondrichthyes.
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PMID:Molecular markers of cancer in cartilaginous fish: immunocytochemical study of PCNA, p-53, myc and ras expression in neoplastic and hyperplastic tissues from free ranging blue sharks, Prionace glauca (L.). 1823 18


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