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)

Four new permanent cell lines (RCC-A, -B, -C, and -D) derived from different human renal cell carcinomas of the clear cell type were established in tissue culture. The cell lines displayed characteristic differences in cell size and shape, which allowed individual identification by phase contrast microscopy. Ultrastructurally, the cell lines exhibited varying amounts of cytoplasmatic glycogen and lipid. Immunohistochemistry revealed co-expression of vimentin and cytokeratin in all cell lines. The mean population doubling time ranged from 27 h (RCC-A) to 104 h (RCC-D). RCC-B and -C cells produced slowly growing tumours after heterotransplantation into nude mice, whereas RCC-A and RCC-D cells were non-tumorigenic. The modal chromosome number was either near-diploid (RCC-A, -B, and -C) or near triploid (RCC-D). Clonal abnormalities affecting the short arm of chromosome 3 were seen in all cell lines. Northern blot analysis revealed no expression of the proto-oncogenes c-fos, c-ros, and c-mos, whereas c-Ki-ras expression was observed in all cell lines. Expression of c-myc was observed in RCC-A, RCC-B, and RCC-D cells, whereas c-raf expression could be detected in RCC-B and RCC-D. Tumour suppressor gene p53 mRNA was observed in the cell line RCC-D.
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PMID:Cytomorphological, cytogenetic, and molecular biological characterization of four new human renal carcinoma cell lines of the clear cell type. 751 57

Activation of cellular oncogenes and inactivation of anti-oncogenes have been postulated as important mechanisms during hepatocarcinogenesis. This study was conducted to detect abnormal levels of several proto-oncogenes (c-jun, c-fos, c-H-ras) and of the p53 and the alpha-fetoprotein gene in the liver during cirrhosis, a pathological process which predisposes to the development of hepatocarcinoma. Liver tissue from 11 patients with cirrhosis of different etiologies, and seven histologically normal liver fragments taken at the periphery of benign liver tumors of metastases were studied. Transcripts of the various oncogenes and of the alpha-fetoprotein gene were detected by in situ hybridization, and the p53 protein was revealed by immunocytochemistry. No overexpression of any of the mRNA tested or of the p53 protein was found in histologically normal liver in contact with benign or metastatic tumors. In contrast, 10 of the 11 specimens with cirrhosis (90.9%) displayed abnormally high levels of c-H-ras transcripts. Five samples with cirrhosis revealed a moderate increase in the level of c-fos mRNA. Only one case and two cases, respectively, exhibited increased levels of c-jun and alpha-fetoprotein mRNA. No cases were positive for the p53 antigen. Liver-cell proliferation, as assessed by immunocytochemistry with the Ki 67 monoclonal antibody, was low in both the group with cirrhosis and the control groups (0.49% and 0.55% positive cells, respectively). These data demonstrate that activation of c-H-ras mRNA is an almost constant finding in hepatocytes of livers with cirrhosis. This gene overexpression is not linked to hepatocellular proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of ras oncogene in livers with cirrhosis. 753 24

We describe the properties of a physiological cell death (PCD)-resistant subline of WEHI-231 generated from the PCD-susceptible WEHI-231.7 JM cell line maintained in our laboratory. The PCD-resistant WEHI-231.7 JMRE subline was uniquely resistant to anti-immunoglobulin (Ig)M-induced PCD but not to irradiation and etoposide. In these sublines, we compared the expression of genes implicated in regulating PCD. Northern analysis of c-myc, c-fos, egr-1, Fas, p53 and retinoblastoma revealed similar basal levels of expression in all sublines tested and comparable responses to anti-IgM treatment. Similarly, the expression of bcl-2, bcl-x, bax and IL-1 beta converting enzyme did not correlate with susceptibility to anti-IgM-induced PCD. Next, we systematically studied signal transduction events including: tyrosine phosphorylation, Ca++ flux, and ceramide production in the Jm and JMRE sublines. The tyrosine phosphorylation patterns and the Ca++ influx generated following sIgM engagement were very similar in the JM and JMRE sublines. In contrast, the generation of ceramide differed in the PCD-resistant and PCD-susceptible sublines. Ceramide is produced following cross-linking sIgM on WEHI-231.7 JM cells and causes PCD. Ceramide levels in anti-IgM-treated WEHI-231.7 JMRE cells are low and appear to be insufficient to induce PCD.
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PMID:Resistance to anti-IgM-induced apoptosis in a WEHI-231 subline is due to insufficient production of ceramide. 753 68

We performed experiments to determine the effects of ionizing radiation exposure on expression of genes such as beta-actin, c-fos, histone H4, c-myc, c-jun, Rb, and p53 after exposure of Syrian hamster embryo (SHE) cells to the protein synthesis inhibitor cycloheximide. The purpose of these experiments was to determine the role of a labile protein in the radiation-induced response. The results revealed that when ionizing radiation (either fission-spectrum neutrons or gamma rays) was administered 15 min after cycloheximide treatment of SHE cells, the radiation exposure reduced cycloheximide-mediated gene induction of c-fos, histone H4, and c-jun. In addition, dose-rate differences were found when radiation exposure most significantly inhibited the cycloheximide response. Our results suggest that ionizing radiation does not act as a general protein-synthesis inhibitor and that the presence of a labile protein is required for the maintenance of specific gene transcription and mRNA accumulation after radiation exposure, especially at high dose-rates.
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PMID:Combined effects of ionizing radiation and cycloheximide on gene expression. 753 71

Human osteosarcoma and fibrosarcoma cell lines were investigated for alterations in oncogenes, tumor suppressor genes, and growth factors, all of which have been implicated in tumor formation. Characterization of oncogenes that are involved in osteosarcoma formation, including the c-fos and c-myc oncogenes, indicated that all six osteosarcoma cell lines examined had 5- to 20-fold amplification of the c-myc oncogene, whereas neither of two fibrosarcoma cell lines c-myc amplification. Interestingly, only three of six osteosarcoma cell lines displayed altered c-myc immediate-early gene function. c-fos was found to be normal, both at the gene and functional levels, in all six osteosarcoma and both fibrosarcoma cell lines tested. Characterization of two tumor suppressor genes, p53 and RB1, that have been implicated in osteosarcoma formation indicated that p53 was altered in five of six osteosarcoma cell lines, whereas RB1 was altered in only two or six of these cell lines. Neither RB1 nor p53 was found to be altered in the fibrosarcoma cell lines tested. An additional transformation marker, autocrine growth-factor production, was observed in all six osteosarcoma cell lines and both fibrosarcoma cell lines examined. Finally, the differentiation state of the osteosarcoma cell lines was investigated via the bone differentiation markers alkaline phosphates and osteocalcin. Alkaline phosphatase activity was observed in four of six osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined. The alkaline phosphatase activity was a result of the expression of the bone/liver/kidney alkaline phosphatase isoform. High-level osteocalcin expression was observed in one of the osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined, although all cell lines demonstrated low-level osteocalcin expression. Together, these data demonstrate that relatively undifferentiated osteosarcomas commonly display c-myc amplification, p53 and RB1 mutation, and autocrine growth-factor production, all of which may play a role in osteosarcomagenesis.
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PMID:Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines. 757 9

The expression of the p53 protein (p53) was compared with those of several oncogenes including c-fos (Fos), c-jun (Jun), and epidermal growth factor receptor (EGFR1) using immunohistochemistry in frozen and paraffin-embedded sections of 25 basal cell carcinomas (BCCs) to find out any correlation between p53 and oncogenes in the pathogenesis of human BCC. In normal skin, positive reactions were obtained for EGFR1 and Fos, while p53 and Jun were negative in all cases. In the lesions, EGFR1 was observed in all cases and p53 was positive in 9 of 25 (36%). Fos was expressed in 21 of 25 (84%) and four negative cases were all p53-positive; this negative correlation between p53 and Fos staining was statistically significant (P < 0.01). Jun was detected in 14 of 20 (70%) and no significant relationship was observed between the expression of Jun and Fos or p53. These data suggest the possibility of down regulation of Fos expression by high levels of p53 protein. Further work is necessary to determine the mechanism of this interaction.
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PMID:Oncogene interaction in basal cell carcinomas of human skin. 757 99

Mechanisms of aging involve genetic programs and error accumulation. Cellular aging is an aspect of organismal aging from a point of view of age-dependent declines of tissue cells during the postreproductive aging process and a parallelism between enhanced individual and cellular aging in some genetic progeroid syndromes. Cellular senescence involves the gene-directed inhibition of replicative potential of cells. Cell fusion analysis has indicated that senescent normal and presenescent Werner syndrome cells cause the dominant suppression of DNA synthesis in the partner of either actively growing cells or any cells of the four complementation groups of immortalized human cells. Membrane proteins produced in senescent cells showed the biphasic DNA synthesis-inhibiting activity when assayed for young cells. Senescent cells showed the strong transcriptional repressions of early serum responsive genes (c-fos, c-jun, c-myc), late responsive genes of transcription factor E2F1 and cyclin E. In addition, the protein levels of CDK2 and cyclin E are also extremely low, with an increased level of the p53-dependent p21 Cip 1 protein which inhibits the kinase activity of cyclins/CDKs by forming complexes. Such characteristic molecular factors and mechanisms feature irreversible G1-arrest in cellular senescence.
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PMID:[Aging and cellular senescence]. 761 77

UVB irradiation inhibits melanocyte proliferation by causing arrest in G1 (D. Barker, K. Dixon, E. E. Medrano, D. Smalara, S. Im, D. Mitchell, G. Babcock, and Z. A. Abdel-Malek. Cancer Res., 55: 4041-4046, 1995). To determine how, after UVB irradiation, signal transduction pathways, DNA damage, and cell cycle arrest interact in the human melanocyte, we analyzed here the possible activation of tyrosine kinases, the serine-threonine kinases Baf-1 and ERK2, the status of the transcription factor c-fos, and the activation of cell cycle checkpoints induced by expression of p53 protein. We found that in contrast to the UVC response, exposure to UVB irradiation did not stimulate the above kinases. UVB light induced a prolonged c-fos expression, suggesting a mechanism of induction different from the transient expression elicited by growth factors. The tumor suppressor p53 and the p53-inducible cyclin-dependent kinase inhibitor protein p21Waf-1/SDI-1/Cip-1 were expressed at high levels for at least 2 days after UV-irradiation. In parallel, phosphorylation of Rb, the retinoblastoma tumor suppressor gene product, was halted in UVB-irradiated cells and correlated with the expression of the protein p21Waf-1/SDI-1/Cip-1. Our data define for the first time how UVB irradiation affects the expression of crucial regulatory events needed for cell cycle progression in the human melanocyte.
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PMID:Ultraviolet B light induces G1 arrest in human melanocytes by prolonged inhibition of retinoblastoma protein phosphorylation associated with long-term expression of the p21Waf-1/SDI-1/Cip-1 protein. 766 78

Systemic administration of kainate induces cell death in vulnerable regions of the rodent brain. Neuronal degeneration is associated with internucleosomal DNA fragmentation and induction of presumptive cell death effector genes (e.g. p53, c-fos) suggesting that kainate activates an apoptotic pathway. In the present study, kainate-induced DNA damage has been demonstrated at the cellular level by in situ nick translation in the mouse hippocampus and neocortex at 24 h and 48 h after intraperitoneal injections. In the same regions, the intensity of Bcl-2 immunoreactivity decreased by about 45% as measured by digital image analysis. Most important, kainate treatment evoked a nearly 3-fold increase in bax mRNA levels within the mouse brain. The down-regulation of bcl-2, which promotes cell survival, and the up-regulation of bax, which promotes programmed cell death, may have functional significance in kainate-mediated excitotoxicity and in the selective vulnerability of specific brain regions.
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PMID:Up-regulation of bax and down-regulation of bcl-2 is associated with kainate-induced apoptosis in mouse brain. 767 27

The effect of vitamin A deficiency on hepatic regeneration in male and female rats was studied after partial hepatectomy. A fourfold increase in the number of positive dUTP end-labeled nuclei was observed in the deficient animals as early as 30 minutes after partial hepatectomy and their number reached a peak by 8 hours after the operation. The bile duct cells were both morphologically and biochemically intact at all time points. Administration of retinyl palmitate 1 hour before partial hepatectomy significantly reduced the number of positive nuclei, and treatment with retinyl palmitate 24 or 48 hours before the operation reduced the number of positive cells to the level observed in control vitamin A-supplemented rats. The level of transcripts for c-jun, c-fos, c-myc, and transforming growth factor-beta 1 were increased for an extended period of time in livers of deficient animals, whereas the expression of both p53 and max were unchanged. Immunocytochemistry demonstrated the presence of latent transforming growth factor-beta 1 in cells showing evident apoptotic or necrotic changes in their nuclei. This study demonstrates the importance of vitamin A for the survival of hepatocytes both in intact vitamin A-deficient liver and after partial hepatectomy, whereas the ductal cells appear to be less sensitive to vitamin A deficiency.
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PMID:Effect of vitamin A deficiency on the integrity of hepatocytes after partial hepatectomy. 767 81


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