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)

The p53 tumor suppressor gene is the most commonly mutated gene in human cancer and is a frequent abnormality in oral squamous cell carcinoma and its precancerous lesions. MDM2 (murine double minute-2), a new proto-oncogene, may be associated with p53 gene products and may negatively affect the transcriptional activating function of p53. The purpose of this study was to investigate the incidence of MDM2 and its relationship to the expression of p53 in oral squamous cell carcinoma and precancerous lesions. Overexpression of p53 and MDM2 proteins was detected in 52 and 40% of oral squamous cell carcinomas, respectively. p53 gene mutation, absent in normal oral epithelium was observed in 31% of the carcinoma cases. Our finding suggested that MDM2 protein may be an alternative mechanism causing p53 protein dysfunction in oral squamous cell carcinoma.
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PMID:p53 and MDM2 expression in oral squamous cell carcinoma. 869 35

Polyomavirus large T-antigen transgenic mice develop cardiac hypertrophy characterized by an increase in atrial natriuretic factor and beta-myosin heavy chain isoform expression. The aim of this study was to examine changes in proto-oncogene expression in hypertrophied hearts from the transgenic mice. Expression of early growth response-1 (Egr-1) mRNA was detected in hearts from all 15 transgenic mice, but was not detectable in 13 control mice. Reverse transcriptase-polymerase chain reaction experiments using Egr-1-specific primers confirmed the increase in Egr-1 mRNA in enlarged hearts from the transgenic mice. Expression of c-jun, junD and Ha-ras mRNAs was increased in the transgenic hearts 3, 17 and 2.8-fold respectively. Western blots showed an increase in c-myc, c-jun and ras protein in hypertrophied transgenic hearts. Immunofluorescence analyses confirmed an increase in Egr-1 and c-jun protein in transgenic cardiomyocytes. Proliferating cell nuclear antigen, Ki-ras and HSP 90 mRNAs were decreased 22, 2.7 and 3-fold, respectively in the transgenic hearts. Not altered in most hypertrophied hearts was expression of c-fos, junB, p53, c-neu, c-myc, HSP70, HSP27, TGF-beta or IGF 1 mRNAs. Proto-oncogene and growth factor gene expression in hypertrophy induced by PVLT expression is modulated with some proto-oncogenes increased and others decreased in expression.
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PMID:Molecular remodelling in hypertrophied hearts from polyomavirus large T-antigen transgenic mice. 875 Nov 59

The expression of the protein products and mRNA of c-fos, c-myc, p53, and c-raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c-fos and c-myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.
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PMID:Proto-oncogene expression in human glomerular diseases. 877 42

Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the sequential alteration of proto-oncogene mRNA expression in liver, spleen, kidney and brain of mice after whole body irradiation (WBI). The mRNAs investigated in this study were Fas, c-fos, c-myc. bcl-2, and p53, and glyceraldehyde-3-phosphate dehydrogenase mRNA was employed as internal control. C3H/He mice aged 9-10 weeks were exposed to WBI of 7 Gy using a cobalt-60 teletherapy unit, without anesthesia, and sacrificed before and 0.1, 0.5, 1, 2, 3, 6, 12, 24, 48 and 96 h after irradiation. Their liver, spleen, kidney and brain were taken and immediately stored in liquid nitrogen until ready for RT-PCR. Each specimen was homogenized to extract RNA for conventional RT-PCR. The liver of mice administered 7 Gy of WBI revealed no significant changes in the expression of each of the mRNAs examined. In the spleen, c-fos mRNA expression decreased at 2 h following irradiation, and increased remarkably thereafter. In the kidney, no significant change in the expression of each mRNA was shown. In the brain c-fos mRNA expression decreased 1-24 h after irradiation, and showed a recovery thereafter. The remarkable differences in the sequential changes of c-fos mRNA expression following irradiation between each organ revealed by the present experiment may be an important aid in determining the tissue-specific radiosensitivity to ionizing radiation. Further investigations are, however, needed to clarify the signal transduction mechanisms which are mediated by the expression of these proto-oncogenes in each tissue following irradiation.
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PMID:Sequential alteration of proto-oncogene expression in liver, spleen, kidney and brain of mice subjected to whole body irradiation. 878 77

The proto-oncogene c-myc has been implicated in both cellular proliferation and apoptosis, and we have shown that overexpression of c-myc can induce polycystic kidney disease in transgenic mice. To elucidate the molecular and cellular defects underlying cystogenesis, we have investigated the potential roles of cell proliferation and apoptosis as they relate to c-myc and modulators of c-myc function in human autosomal dominant polycystic kidney disease (ADPKD). Renal c-myc expression was consistently elevated, up to 15-fold, in ADPKD. High levels of c-myc expression correlated with 10- to 100-fold increased proliferation index in cystic epithelium. Interestingly, steady-state levels of bcl-2 mRNA were also increased up to 20-fold and Bcl-2 protein was markedly elevated. In contrast, the expression of bax and p53 was virtually unchanged. However, apoptosis was consistently and significantly increased in ADPKD kidneys, unchecked by high levels of Bcl-2. Together with proliferation, apoptosis may thus represent a general mechanism for cyst growth and tissue remodeling. We conclude that both epithelial cell proliferation and apoptosis required for normal kidney homeostasis are deregulated in ADPKD, recapitulating the renal developmental program. Furthermore, abnormal expression of proto-oncogenes regulating these processes is an important mediator of cystogenesis in human ADPKD.
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PMID:Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). 880 89

The aim of this study was to investigate bcl-2 expression in head and neck cancer patients and to investigate its correlation with biological and clinical characteristics and outcome of accelerated radiotherapy. A series of 93 patients with squamous cell carcinoma of the head and neck who had been uniformly treated with continuous hyperfractionated accelerated radiation treatment (CHART) were investigated. These patients had also been injected with bromodeoxyuridine (BrdUrd) to measure cell kinetic parameters using flow cytometry (FCM) and their p53 protein status had also previously been described. Bcl-2 expression was assessed using immunohistochemistry. Sixteen of the 93 (17.2%) patients stained positively for bcl-2 proto-oncogene. The percentage of positive tumour cells within the specimens was highly variable, ranging from a few percent to complete positivity. Bcl-2 positivity was correlated with improved local control (p > 0.0016) and survival (p > 0.012) in comparison with non-expressing tumours. There was no correlation between bcl-2 expression and histological grade, T stage or site but overexpressors were almost exclusively node negative. The significance of bcl-2 was reduced when node negative tumours were analysed alone. There was no correlation of bcl-2 with p53 expression but there was a trend for overexpression to be associated with diploidy and rapidly proliferating tumours. These data suggest that bcl-2 expression in head and neck cancer is not associated with disease progression.
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PMID:Bcl-2 expression correlates with favourable outcome in head and neck cancer treated by accelerated radiotherapy. 881 42

We tested the effects of theophylline, a phosphodiesterase inhibitor inducing intracellular accumulation of cyclic adenosine monophosphate (cAMP), on malignant B cells from 15 patients with B-chronic lymphocytic leukemia (B-CLL). We observed a large increase in apoptotic cell numbers (mean, 90% v 20% in medium alone) in the presence of theophylline (100 micrograms/mL) or chlorambucil (10 mumol/L) after 72 hours of incubation. Maximal apoptosis (90%) was reached after 36 hours when the two drugs were used together at fourfold lower concentrations, indicating a synergistic effect; no effect was observed with normal B cells, suggesting that the combination might have therapeutic interest. Chlorambucil induced intracellular Ca+2 influx, pointing to the involvement of two signaling pathways that might explain its synergy with theophylline through their effects on oncogenes. The expression of bcl-2 protein, a proto-oncogene inhibiting apoptosis, decreased after incubation with the drugs, while c-myc, recently described as having a potent role in apoptosis, was overexpressed. For p53 we observed an overexpression in the presence of chlorambucil or both theophylline-chlorambucil and a decrease after theophylline incubation. Chlorambucil- and theophylline-induced apoptosis was partially inhibited by interleukin-4 (IL-4), which also abrogated the effects on oncogene expression. These results provide insight into the mechanisms underlying B-CLL apoptosis and suggest that the theophylline-chlorambucil combination may be of therapeutic value in this setting.
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PMID:Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells. 882 37

bcl-2 is a proto-oncogene which inhibits apoptosis. In contrast, p53 tumour suppressor gene is known to induce apoptosis. In this study we analysed immunohistochemically 63 mesenchymal tumours for the expression of bcl-2 and p53 proteins with a special emphasis on muscle-derived tumours. bcl-2 was expressed in all seven rhabdomyosarcomas and in five out of seven leiomyosarcomas. In benign muscle tumours, bcl-2 expression was found in all four epithelioid leiomyomas and in six out of 14 leiomyomas. In non-neoplastic muscle cells, occasional weak bcl-2 positivity was found in muscle cells of vascular walls and myometrium. In mesenchymal tumours of other lineages, bcl-2 positivity was only found in four out of 12 malignant fibrous histiocytomas and in one out of three liposarcomas. p53 positivity was found in 14 tumours, 13 of which were sarcomas. No association was found between p53 and bcl-2 positivity. Our results suggest that bcl-2 expression is activated significantly more often in muscle derived tumours than in mesenchymal tumours of other lineages. Our results also suggest that p53 status does not directly affect the expression of bcl-2 in sarcomas.
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PMID:bcl-2 is preferentially expressed in tumours of muscle origin but is not related to p53 expression. 883 22

In an effort to understand the role of specific fats on carcinogenesis, we have studied the effects of lipids derived from cancer patients on components associated with the regulation of proliferation. The treatment of tumor cells with patient-derived fats produced increased cell proliferation, as indicated by shorter doubling times. The effects of patient-derived lipids on the expression of ras, c-jun, c-erbB-2, and p53 gene products were examined. The cellular expression of the ras proto-oncogene product was increased in both colon tumor cell lines, following lipid treatment. However, c-jun proto-oncogene expression was elevated in HT-29 cells and appeared unchanged in SK-Co-1 cells after lipid treatment. Treatment of HT-29 tumor cells with patient-derived fats produced an enhancement of the p53 gene product, whereas fat treatment reduced p53 expression in SK-Co-1 tumor cells. Further separation of the patient-derived fats indicated that the amplification of p53 gene expression in HT-29 cells could be achieved primarily by addition of the diacylglycerides fraction. Addition of the purified fatty acids, comprising the diglyceride fraction, indicated that the fatty acids, 16:1, 18:0, and 18:1, induced the most significant increases in p53 expression by HT-29 cells. These alterations caused by cancer patient-derived fats are consistent with the loss of normal growth regulation and may explain the epidemiologic association between certain fats and carcinogenesis.
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PMID:Modulation of colon tumor oncogene expression by cancer patient-derived lipids. 884 66

Changes in gene expression including that of c-fos occur following cerebral ischemia. Proto-oncogenes c-myc and s-myc and oncosuppressor gene p53 are known to induce apoptosis in some types of cells, whereas proto-oncogene bcl-2 inhibits apoptosis. Possible induction of mRNAs for c-myc, N-myc, s-myc, c-fos, p53 and bcl-2 was examined following focal ischemia in the rat anterior cortex, hippocampus, thalamus and cerebellum by Northern blot analysis. Animals were decapitated 1, 2, 6, 12, and 24 hours following the left middle cerebral artery (MCA) occlusion. In sham-operated control rats, the mRNAs for c-myc, N-myc, c-fos and p53 were present in the anterior cortex, hippocampus, thalamus on both sides, and in the cerebellum, whereas those for s-myc and bcl-2 were not. The c-myc gene expression was rapidly and markedly induced by the MCA occlusion in the ipsilateral anterior cortex, hippocampus and thalamus in a time-dependent manner. In these regions, the c-fos gene expression was also induced as early as 1 hour after the MCA occlusion. The p-53 mRNA was induced in the ipsilateral hippocampus at 24 hours after MCA occlusion. In contrast, mRNAs for N-myc, s-myc and bcl-2 were not induced following MCA occlusion. These results indicate a possibility that high-level expression of the c-myc gene may be involved in the ischemic cellular events including apoptosis.
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PMID:Up-regulation of c-myc gene expression following focal ischemia in the rat brain. 898 58


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