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)

Ultrastructural, flow cytometric, and molecular studies were performed on leukemia cells from bone marrow and pleural effusion of a 6-year-old boy diagnosed with undifferentiated (MO) leukemia, using routine histology and immunostains at diagnosis and relapse. Ultrastructurally, surface and/or intracellular ferritin particles were present on or in some blasts and the majority of blasts contained identifiable acid ferrocyanide reactive inorganic iron comparable to that seen in normal early erythroblasts. The cells lacked other evidence of differentiation, including diaminobenzidine-reactive or immunoreactive hemoglobin. Flow cytometric analysis of malignant cells showed a lack of lymphoid or myeloid markers. Anti-transferrin receptor antibody was positive on 93% of cells and antibody to glycophorin A reacted with 23% of cells. RNA blot analysis of leukemia cells with myeloperoxidase (MPO) showed an absence of appreciable levels of MPO mRNA. Chromosome analysis showed 51,XY, t(1;16)(p31;q24), +6, +10, +15, +19, +21. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells and produces a DNA-binding protein responsible for myeloid differentiation, was found to be duplicated in the patient's tumor cells. Expression of c-jun, N-ras, c-myc, and p53 was normal. The data indicate that the malignant cells in this patient are of early erythroid lineage at diagnosis and relapse and that classification of cell lineage can be enhanced by ultrastructural Prussian blue staining. The failure of this otherwise undifferentiated leukemia to express or evolve into a myeloid phenotype is biologically and clinically distinct from previously described cases of erythroid and myeloid leukemia and may represent a previously unidentified phenotype which should be included in the spectrum of 'undifferentiated' childhood leukemia.
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PMID:Childhood undifferentiated leukemia with early erythroid markers and c-myb duplication. 170 34

We have activated resting human T lymphocytes to study the roles of the putative cell cycle control gene products, retinoblastoma susceptibility gene product (Rb) and p53, in regulating cell proliferation. After stimulation with phorbol, 12,13, dibutyrate and the calcium ionophore, ionomycin, which triggers a rapid entry of cells into G1 phase, we demonstrated Rb phosphorylation 24 h later, well before the onset of DNA synthesis. This finding, in contrast to reports using proliferating cell lines, implies that Rb phosphorylation is not a proximal event regulating the G1 to S transition. The production of p53 became detectable 3 to 6 h after addition of phorbol, 12,13,-dibutyrate and ionomycin, and peaked at 30 to 42 h. To further delineate the relationship of the synthesis and metabolism of the proteins to cell cycle progression, we used three agents to arrest progression of activated T cells at various points in the cell cycle. Aphidicolin arrested the cells at the G1/S boundary, whereas deferoxamine, an iron chelator, arrested the cells at an earlier stage of the cell cycle. Cyclosporin A blocked T cell activation at the earliest point in the cell cycle. In the presence of aphidicolin, Rb phosphorylation and p53 production proceeded normally whereas cyclosporin A inhibited both events. Although deferoxamine completely prevented Rb phosphorylation, p53 production was unaffected, suggesting a differential regulation of the two molecules. Our results place Rb phosphorylation and p53 production in the hierarchy of genetic events that are thought to regulate T lymphocyte progression through the cell cycle.
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PMID:Differential regulation of the tumor suppressor molecules, retinoblastoma susceptibility gene product (Rb) and p53, during cell cycle progression of normal human T cells. 190 3

Ribonucleotide reductase consists of two non-identical protein subunits that are required for enzyme activity. These subunits are encoded by different genes and are not expressed coordinately as the cells pass through the cell cycle. Using specific cDNAs for the non-heme iron (NHI) and the effector-binding (EB) subunits the levels of the mRNAs for these two subunits were determined in leukemia L1210 cells during the transition from the G0/G1 phase to the S and G2/M phases of the cell cycle. Synchronized populations of L1210 cells were obtained either by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) treatment or by enrichment by elutriation centrifugation. The changes in the levels of the mRNAs for NHI and EB subunits were compared with the changes in the levels of the mRNAs for actin, p53, c-myc, thymidine incorporation into DNA, and DNA content by flow cytometric measurements. Synchronization of the cells by the two methods resulted in quantitative differences in the responses. The EGTA synchronized L1210 cells showed maximal increases of 9.3- and 5.7-fold in the mRNAs for the NHI and EB subunits, respectively. The peak level of the NHI mRNA was observed at 12 hr after the addition of calcium ions. The peak increase in the level of the mRNA for the EB subunit was observed between 12 and 15 hr after the addition of calcium ions. The rate of increase for the mRNA for c-myc was greater than the increase in the mRNA for the NHI subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in messenger RNA levels for the subunits of ribonucleotide reductase during the cell cycle of leukemia L1210 cells. 270 Sep 14

To better understand diseases of the thoracic space, pathologic findings of thoracoscopic open lung biopsy are described based on thoracoscopic anatomy and pleural mesothelioma. A positive colloidal iron stain in the plasma membrane of the mesothelial cells indicates the presence of hyaluronic acid, which appeared to decrease the friction between the lung and thoracic cavity. Excess fluid in the pleural cavity was removed from specific sites in the parietal pleura with stomas. We evaluated the pathologic features of 57 video-thoracoscopic open lung biopsies. Specific diagnoses were established in 89%, and of these half were pneumothorax. Nonspecific pathologic changes were found in 11%, of which interstitial pneumonia was the most common. This procedure is useful in taking a large number of specimens for diagnosis, and to evaluate the degree and progress of fibrosis. The differential diagnosis of mesothelioma from pulmonary adenocarcinoma, reactive mesothelial hyperplasia, and sarcoma of the pleura are described. Also, to understand mutations of the p53 tumor-suppressor gene in mesothelioma, mesothelial lesions were studied with immunostaining for p53 antibody (DO-7) and with in situ hybridization for p53 mRNA. In immunohistochemical staining for DO-7, all reactive mesothelial cells were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive. mRNA for p53 was expressed in all reactive mesothelial cells, and in 55% of allmesotheliomas.
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PMID:[Thoracoscopic anatomy, significance of pathologic findings in thoracoscopic open lung biopsy, and pleural mesothelioma]. 760 22

Primary lung carcinomas often carry mutations in the p53 tumor suppressor gene. Most of these mutations alter the conformation of the p53 protein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chromosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclonal antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their anamnestical asbestos exposure. Presence of asbestos bodies (AB) was evaluated from histologic samples of peripheral nontumorous lung tissue using both 5-microns-thick sections stained with Perls' iron and 30-microns-thick unstained sections. Abnormal accumulation of p53 protein was found in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the asbestos content of lung tissue: 35% of the p53-positive patients had more than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046). Patients with strongly p53-positive tumors were heavier smokers (57.2 +/- 38.2 pack-years) than patients with p53-negative or lightly positive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.
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PMID:p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke. 804 41

Previous studies have shown renal mesenchymal tumors (RMTs) induced in rats by a single intrarenal injection of nickel subsulfide and iron are more pleomorphic and metastatically aggressive than RMTs induced by a single ip injection of methyl(methoxymethyl)nitrosamine (DMN-OMe). While both RMT types contain high levels of K-ras activation, the specific mutational spectra within codon 12 of K-ras are quite different. Nickel subsulfide and iron-induced tumors exhibited codon 12 GGT-->GTT transversions exclusively, while DMN-OMe RMTs showed a wide array of codon 12 mutations, as well as mutations within codons 61 and 63 [K. G. Higinbotham, J. M. Rice, B. A. Diwan, K. S. Kasprzak, C. D. Reed, and A. O. Perantoni, Cancer Res., 52: 4747-4751, 1992; K. G. Higinbotham, J. M. Rice, and A. O. Perantoni, Mol. Carcinog., 5: 136-139, 1992]. In an effort to further correlate carcinogen-specific molecular events in renal tumors, we investigated the p53 tumor suppressor gene in RMTs induced by these two carcinogens for the presence of point mutations. The evolutionarily conserved portion of the coding region of the gene, including part of exon 4 through exon 10, was surveyed for point mutations utilizing single-strand conformation polymorphism and chemical cleavage of mismatches analyses. None (0 of 10) of the nickel subsulfide and iron-induced RMTs and only 1 of 10 DMN-OMe-induced tumors that were evaluated contained point mutations within this portion of the p53 gene. Direct sequencing of the one single-strand conformation polymorphism and chemical cleavage of mismatches-"positive" DMN-OMe-induced RMT revealed a GCC-->GTC (Ala-->Val) transition in codon 345 within exon 10. These results suggest that the different tumorigenic phenotypes exhibited by these two RMTs are not the result of specific mutations or patterns of mutations within the portion of the p53 gene examined and that the mutated p53 tumorigenic pathway, whereby p53 plays a major role in many human neoplasms, does not function in RMTs induced by either agent.
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PMID:Low incidence of point mutations detected in the p53 tumor suppressor gene from chemically induced rat renal mesenchymal tumors. 826 41

Deferoxamine (DFO)-induced iron deprivation caused an increase in p53 expression in ML-1 and Raji cells. In ML-1 cells, with express wild type p53, p53 protein levels were transiently increased 6 h after addition of 10(-4)M DFO. In Raji cells, which carry a mutant p53 allele, p53 increased 6 h after addition of 10(-4)M DFO and remained elevated for 24 h. Growth inhibition was observed in both cell types 6 h after addition of 10(-4)M DFO. In both cells, p53 mRNA levels did not increase following incubation with DFO, suggesting that increased p53 expression is the result of a post-transcriptional mechanism. Although increases in wild type p53 protein in ML-1 cells resulted in increases in a p53 target gene, p21cipl/wafl/sdil, this effect was not observed in Raji cells which express a mutant p53 protein.
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PMID:Iron deprivation results in an increase in p53 expression. 859 Jun 32

In order to ascertain whether genetic alterations occur during the early stages of gastric carcinogenesis, abnormal accumulation of p53 protein and mutation of its gene in stomach tissue showing intestinal metaplasia were investigated using immunohistochemistry and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Immunohistochemistry detected 19 foci showing nuclear accumulation of p53 protein in non-neoplastic gastric mucosa in a total of 756 sections (477 of which contained intestinal metaplasia) from 16 resected stomachs containing gastric adenocarcinomas. Of these 19 p53-positive foci, 17 were diagnosed histologically as incomplete-type intestinal metaplasia and 2 as pseudopyloric glands in the regenerative mucosa. Furthermore, 14 such foci were detected in 6 patients with multiple gastric cancers. No correlation between high-iron diamine (HID)-positive sulfomucin production and p53-positive glands was observed. The DNAs were extracted selectively from these p53-positive metaplastic glands and examined for p53 mutations by PCR-SSCP analysis followed by direct sequencing. In only 10 lesions could exons; 5 to 8 be investigated completely, and of these, 4 were shown to possess p53 mutations, which were on exon 5 in 3 cases and on exon 7 in 1 case. These results indicate that irreversible genetic changes had already occurred in morphologically non-neoplastic gastric mucosa with intestinal metaplasia, and are consistent with the hypothesis that intestinal metaplasia, especially the incomplete type, may contain precursor lesions of gastric cancer.
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PMID:p53 mutations in the non-neoplastic mucosa of the human stomach showing intestinal metaplasia. 860 55

Renal cell carcinomas induced in male Wistar rats by iron chelate of nitrilotriacetate (Fe-NTA) were examined for mutations in ras oncogenes and p53 tumor suppressor gene. Fourteen primary tumors and two metastatic tumors from 11 animals were evaluated. Exons 1 and 2 of the H-, K-, and N-ras genes were amplified by polymerase chain reaction (PCR), and the presence of mutations was examined by direct sequencing. Exon 5 through exon 7 of p53 gene, including the 3' half of the conserved region II and the entire conserved region III through V, were surveyed for point mutations by PCR-single stranded conformation polymorphism (SSCP) analysis. Direct sequencing of the ras genes showed no mutations in codon 12, 13, or 61 among the tumors evaluated. SSCP analysis of p53 gene exon 6 indicated conformational changes in two primary tumors. One tumor had a CCG-to-CTG transition at codon 199, and the other had an ATC-to-att transition at codon 229 and two nonsense C-to-T transitions. These results suggest that neither ras genes nor p53 gene play a major role in the development of renal cell carcinomas induced by Fe-NTA.
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PMID:Absence of ras mutations and low incidence of p53 mutations in renal cell carcinomas induced by ferric nitrilotriacetate. 863 2

An iron chelate, ferric nitrilotriacetate (Fe-NTA, induces renal proximal tubular damage, a consequence of iron-catalyzed free radical reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Previous studies have identified, within 24 h after administration of Fe-NTA, lipid peroxidation products, aldehyde-modified proteins and a variety of modified DNA bases such as 8-hydroxyguanine that may be mutagenic in vivo. In the present study, pathological features of the RCCs were studied, and, in an effort to correlate them with carcinogen-specific molecular events in Fe-NTA-induced carcinogenesis, the H-, K- and N-ras oncogenes and the p53 tumor suppressor gene were investigated for the presence of mutations. Fe-NTA-induced RCCs showed similarity to human RCCs in that they are often invasive, metastatic and fatal. None (0 of 12) of the tumors had mutation in codons 12, 13 and 61 of the H-, K- and N-ras genes by direct sequencing. Only one (1 of 12) tumor with high grade histology revealed a CGC-to-CTC (Arg to Leu) transversion in codon 246 of the p53 gene by the use of single strand conformation polymorphism (SSCP) analysis and direct sequencing. High expression of mutant p53 protein was confirmed by Western blotting and immunohistochemistry. Study of three peritoneal mesotheliomas induced by Fe-NTA revealed no mutation in ras and p53 genes. These results suggest that the ras and p53 genes are not the major targets of mutation in Fe-NTA-induced carcinogenesis of kidney and mesothelium. Instead, p53 mutation may work for potentiation of malignant character in Fe-NTA-induced renal carcinogenesis.
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PMID:Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate. 863 3


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