Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the levels of mRNAs encoding ion transporters (ATP1B1, NHE1, NKCC1), beta-actin, GAPDH, regulators of proliferation and apoptosis (p53, Bcl-2) and kinase hSGK, involved in cell water regulation, were studied using RT PCR in the peripheral human lymphocytes activated with phytohemagglutinin for 4-24 h. The common, "grouped", effect that was found was an increase in the levels of the studied mRNAs after an 8 h activation, sometimes preceded by a delay or slight decrease at the initial stage of 0-4 h. Apart from the common features, some differences were observed in the time courses and amplitudes of the responses of individual mRNAs. The arrangement of the individual mRNA responses in lymphocytes from different donors could differ significantly, thus indicating differential regulation of the studied mRNAs apart from the "grouped" effect. The data obtained confirmed our suggestion that regulation of ion transport at the level of mRNA could be involved in the changes of ion balance at the late stage of lymphocyte activation.
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PMID:[Cell cycle and formation of active form of oxygen in rodent fibroblasts]. 1153 80

Hydrostatic pressure (HP) is thought to increase within cartilage extracellular matrix as a consequence of fluid flow inhibition. The biosynthetic response of human articular chondrocytes to HP in vitro varies with the load magnitude, load frequency, as well as duration of loading. We found that continuous cyclic HP (5 MegaPascals (MPa) for 4 h; 1 Hz frequency) induced apoptosis in human chondrocytes derived from osteoarthritic cartilage in vitro as evidenced by reduced chondrocyte viability which was independent of initial cell densities ranging from 8.1 x 10(4) to 1.3 x 10(6) cells ml(-1). HP resulted in internucleosomal DNA fragmentation, activation of caspase-3, and cleavage of poly-ADP-ribose polymerase (PARP). At the molecular level, induction of apoptosis by HP was characterized by up-regulation of p53, c-myc, and bax-alpha after 4 h with concomitant down-regulation of bcl-2 after 2 h at 5 MPa as measured by RT-PCR. In contrast, beta-actin expression was unchanged. Real-time quantitative RT-PCR confirmed a HP-induced (5 MPa) 1.3-2.6 log-fold decrease in bcl-2 mRNA copy number after 2 and 4 h, respectively, and a significant increase (1.9-2.5 log-fold) in tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) mRNA copy number after 2 and 4 h, respectively. The up-regulation of p53 and c-myc, and the down-regulation of bcl-2 caused by HP were confirmed at the protein level by Western blotting. These results indicated that HP is a strong inducer of apoptosis in osteoarthritic human chondrocytes in vitro.
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PMID:Hydrostatic pressure induces apoptosis in human chondrocytes from osteoarthritic cartilage through up-regulation of tumor necrosis factor-alpha, inducible nitric oxide synthase, p53, c-myc, and bax-alpha, and suppression of bcl-2. 1239 8

It has been reported that tumor suppressor gene p53 regulates vascular endothelial growth factor (VEGF) expression, but the relation between them in endometrial carcinoma remains unclear. We investigated VEGF expression in 11 endometrial carcinoma cell lines and the effect of p53 gene transfection on VEGF expression in the p53-mutated endometrial carcinoma cell line, HEC-50B. Immunoblotting for detecting VEGF, p53, and beta-actin was performed. Wild type p53 gene was transfected using the SuperFect method. The mean VEGF value of 0.8 +/- 0.3 (n = 6) in p53 wild-type group was significantly lower than the 1.6 +/- 0.8 (n = 5) that was found in the p53 mutant group (P < 0.05). Levels of VEGF in the culture medium were measured by enzyme immunoassay (EIA). VEGF levels in the p53 gene-transfected HEC-50B cells and the conditioned medium were decreased at 48 h after p53 gene transfection. VEGF expression was downregulated by p53 in endometrial carcinoma cells.
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PMID:Effect of p53 gene transfection on vascular endothelial growth factor expression in endometrial cancer cells. 1278 15

This study investigated potential markers within chromosomal, mitochondrial DNA (mtDNA) and ribosomal RNA (rRNA) with the aim of developing a DNA based method to allow differentiation between animal species. Such discrimination tests may have important applications in the forensic science, agriculture, quarantine and customs fields. DNA samples from five different animal individuals within the same species for 10 species of animal (including human) were analysed. DNA extraction and quantitation followed by PCR amplification and GeneScan visualisation formed the basis of the experimental analysis. Five gene markers from three different types of genes were investigated. These included genomic markers for the beta-actin and TP53 tumor suppressor gene. Mitochondrial DNA markers, designed by Bataille et al. [Forensic Sci. Int. 99 (1999) 165], examined the Cytochrome b gene and Hypervariable Displacement Loop (D-Loop) region. Finally, a ribosomal RNA marker for the 28S rRNA gene optimised by Naito et al. [J. Forensic Sci. 37 (1992) 396] was used as a possible marker for speciation. Results showed a difference of only several base pairs between all species for the beta-actin and 28S markers, with the exception of Sus scrofa (pig) beta-actin fragment length, which produced a significantly smaller fragment. Multiplexing of Cytochrome b and D-Loop markers gave limited species information, although positive discrimination of human DNA was evident. The most specific and discriminatory results were shown using the TP53 gene since this marker produced greatest fragment size differences between animal species studied. Sample differentiation for all species was possible following TP53 amplification, suggesting that this gene could be used as a potential animal species identifier.
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PMID:A molecular genetic approach for forensic animal species identification. 1285 Apr 2

A key issue in cancer biology is whether genetic lesions involved in tumor initiation or progression are required for tumor maintenance. This question can be addressed with mouse models that conditionally express oncogenic transgenes, i.e., under the control of tetracycline (tet)-dependent transcriptional regulators. We have developed a system for studying tumor maintenance by using avian retroviral [i.e., replication-competent avian leukosis virus long terminal repeat with splice acceptor (RCAS)] vectors to deliver the reverse tet transcriptional transactivator (rtTA) gene to somatic mammalian cells. rtTA can regulate any transgene in which the protein coding sequence is preceded by a tet-operator (tet-o); RCAS viruses infect only cells engineered to express ectopically the avian retroviral receptor, TVA. One vector, RCAS-rtTA-IRES-GFP, also encodes GFP to identify infected cells. Infection of cells from beta-actin TVA transgenic mice with this vector permits efficient regulation of tet-responsive transgenes. Sarcomas arise when p53-deficient murine embryonic fibroblasts carrying beta-actin TVA and tet-o-K-ras4bG12D transgenes are infected with RCAS-rtTA-IRES-GFP and introduced into nude mice treated with the tet analog, doxycycline (dox); when dox is withdrawn, K-ras4bG12D levels fall, cells undergo apoptosis, and tumors regress. Regression can be prevented by means of a genetic complementation assay in which tumors are superinfected before dox withdrawal with other RCAS viruses, such as those carrying an active allele of K-ras. Many TVA and tet-regulated transgenic mice have been generated; thus, this method for somatic cell-specific and temporally controlled gene expression may have broad applications for the study of oncogenesis and tumor maintenance, as well as other cell functions and development.
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PMID:Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance. 1285 57

Vascular endothelial growth factor (VEGF) that activates endothelial cell growth induces angiogenesis, which is indispensable to tumor igenesis and tumor progression. On the other hand, tumor suppressor gene p53 has been considered to regulate VEGF expression, but the detailed relationship between them remains unclear. In this study, we aimed to study VEGF expression in endometrial carcinoma cells and the effect of p53 gene transfection on VEGF expression using p53-mutated endometrial carcinoma cell line, HEC-50B. Immunoblotting for detecting VEGF protein, p53 protein and beta-actin was performed using 11 endometrial carcinoma cell lines. Levels of VEGF in the cultured media were measured by Enzyme immunoassay(EIA). Transfection of wild p53 gene was carried out by SuperFect method in HEC-50B cells, which had mutant p53 gene and did not express p53 protein. The results of immunoblotting were analyzed by NIH image and expressed as values. The results of EIA were expressed as the relative value. The VEGF value was 0.8 +/- 0.3 (n = 6) in p53-wild group, whereas in p53-mutant group it was 1.6 +/- 0.8 (n = 5). VEGF expression was correlated significantly with p53 status (P < 0.05). VEGF levels in p53 gene-transfected cells and the conditioned medium were decreased in 48 hours after p53 gene transfection. VEGF expression was down-regulated by p53 in endometrial carcinoma cells.
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PMID:VEGF expression and its reguration by p53 gene transfection in endometrial carcinoma cells. 1297 25

Sodium cyanide (NaCN)-induced chemical hypoxia is known to increase intracellular free calcium concentration and reduce cell survival, but its effect on gene expression has not been studied. In this study, we designed primers to conduct a rapid and reliable assay for the expression of mRNA of inducible nitric oxide synthase (iNOs), tumor suppressor protein p53, Bcl-2, heat shock protein 70 (HSP-70), and beta-actin in human intestinal epithelial T84 cells and Jurkat T cells. NaCN-induced chemical hypoxia increased iNOs and HSP-70 mRNA in both types of cells, whereas p53 and Bcl-2 mRNA were singularly induced in T84 cells and Jurkat T cells, respectively. In both cell types, treatment of hypoxic cells with a reversible selective iNOs inhibitor, Now-nitro-L-arginine (LNNA), blocked iNOs, Bcl-2, and HSP-70 mRNA, but increased p53. The NaCN-induced hypoxia was also found to increase caspase-3 cellular activity in both cell types. Treatment with LNNA alone decreased the basal caspase-3 cellular activity. A prior treatment of LNNA significantly inhibited the NaCN-induced increase in the cellular activity of this apoptotic enzyme. This is the first report to show that NaCN-induced chemical hypoxia alters both stress-related gene expression and caspase-3 cellular activity and can be regulated by the iNOs inhibitor LNNA. Since NaCN has been included in the 'National chemical terrorism threat' list, by the US Department of Defense, our studies provide useful insight in the development of molecular sensors to detect early exposure to this chemical terrorism threat.
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PMID:NaCN-induced chemical hypoxia is associated with altered gene expression. 1467

Early diagnosis of lung carcinoma is greatly desired. A potential source of early information regarding the process of cancerisation in the airways is exhaled breath condensate (EBC). The direct approach to detecting cancerisation is examining DNA from the area of chronic damage, i.e. airways and lung parenchyma. We therefore investigated DNA in EBC of patients with NSCLC and healthy volunteers. Human DNA was amplified by PCR in exhaled breath condensate and used to detect p53 mutations. A PCR of the beta-actin gene fragment was used to detect human DNA in each of the EBC samples. In 65.7% of the samples, the beta-actin gene was found. Extracted DNA as well as native EBC were equally suited as starting material for amplification. Mutations of the p53 gene were investigated in all EBC samples of NSCLC patients. p53 exons 5-8 were amplified using nested PCR and subsequently sequenced. Mutations were found in four of the patients (n=11; 36.4%) while no mutation was found in volunteers (n=10). Mutations detected in EBC were also compared with those of corresponding tumor tissue. Different point mutations in EBC and tumor tissue were revealed in all cases. Our findings demonstrate that exhaled breath condensate may be used for analysis of somatic gene mutations in an area of direct tobacco-related DNA damage.
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PMID:Detection of p53 gene mutations in exhaled breath condensate of non-small cell lung cancer patients. 1473 43

1. Autistic disease (AD) is a severe neuropsychiatric disorder affecting 2-4 children per 10,000. We have recently shown reduction of Bcl-2 and increase in P53, two important markers of apoptosis, in parietal cortex of autistic subjects. 2. We hypothesized that brain levels of Bcl-2 and P53 would also be altered in superior frontal cortex and cerebellum of age-, sex, and postmortem-interval (PMI)-matched autistic subjects (N = 5 autistic, N = 4 controls). 3. Brain extracts were prepared from superior frontal cortex and cerebellum and subjected to Western blotting. 4. Results showed that levels of Bcl-2 decreased by 38% and 36% in autistic superior frontal and cerebellar cortices, respectively when compared to control tissues. By the same token, levels of P53 increased by 67.5% and 38% in the same brain areas in autistic subjects vs. controls respectively. Calculations of ratios of Bcl-2/P53 values also decreased by 75% and 43% in autistic frontal and cerebellar cortices vs. controls respectively. The autistic cerebellar values were significantly reduced (p < 0.08) vs. control only. There were no significant differences in levels of beta-actin between the two groups. Additionally, there were no correlations between Bcl-2, P53, and beta-actin concentrations vs. age or PMI in either group. 5. These results confirm and extend previous data that levels of Bcl-2 and P53 are altered in three important brain tissues, i.e. frontal, parietal, and cerebellar cortices of autistic subjects, alluding to deranged apoptotic mechanisms in autism.
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PMID:Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices of autistic subjects. 1496 81

The recent observation that studies of BRCA1-associated tumors contain a high proportion of medullary carcinomas and ductal carcinomas with medullary features has re-introduced pathologists to an old diagnostic problem. The term "medullary carcinoma" dates to the 19th century, but the modern entity was introduced in 1949 by Moore and Foote, who described a carcinoma with a lymphoid infiltrate, a favorable prognosis, and low frequency of metastasis. Almost three decades later, Ridolfi et al proposed specific criteria for diagnosis, resulting in an entity with an even more favorable prognosis and a lower incidence. The reproducibility and clinical relevance of the diagnosis have been questioned recently, and new criteria have been proposed and compared. The tumors typically express cytokeratin 7, often vimentin and S100-protein, but not cytokeratin 20. The usual ones are positive for p53 and negative for estrogen receptor, Her2/neu, and bcl-2. Medullary carcinomas express e-cadherin and beta-catenin more often than ordinary high-grade ductal carcinomas, and the former have genetic differences from the latter. The lymphoid infiltrate of medullary carcinomas is related to beta-actin fragments exposed by apoptotic cells. The present review discusses historical and recent developments and emphasizes diagnostic criteria.
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PMID:Medullary carcinoma, provocative now as then. 1507 61


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