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)

We investigated the immunohistochemical expression of p21/waf1 protein in 59 cases of nasopharyngeal carcinomas (NPC) and compared p21 expression with PCNA, p53 and mdm2 protein expression. We found p21, PCNA, p53 and mdm2 in 59/59, 59/59, 18/59 and 12/59 nasopharyngeal carcinomas, respectively. We observed a tendency to a relationship between high expression of PCNA (> 25% positivity in tumour cells) and low expression of p21 protein. Parallel p53/p21 protein expression was found in 18 cases. Twelve were also mdm2 positive. This pattern may represent NPC with wild type (wt) p53 since mdm2 and p21 proteins are inducible by wt p53 gene. In these cases p53 protein expression may be due to stabilisation to mdm2 protein. This could be important in the pathogenesis of these cases since mdm2 may deregulate the p53-dependent growth suppressive pathway. Discordant p53-/p21+ protein expression was found in 41 cases. All were also mdm2 negative. This pattern suggests immunohistochemically undetectable wt p53 gene which is able to induce p21 protein expression.
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PMID:P21/waf1 protein expression in nasopharyngeal carcinoma. Comparative study with PCNA, p53 and MDM-2 protein expression. 925 90

We analyzed G1 accumulation induced by the iron chelator deferoxamine B mesylate (DFO) compared it with that caused by etoposide and cytosine arabinoside (AraC). The results showed that p53 protein increased with all three treatments without an increase in p53 mRNA. After treatment for 3 or 6 h, p21 mRNA increased with 10(-4) DFO to 159% or 556% of pretreatment levels, to 509% or 391% with 10(-5) etoposide, and to 263% or 304% with 10(-5) AraC. Induction of p21 protein was not observed with fluorescence activated cell sorting and Western blot analysis after treatment with DFO or AraC. Treatment with DFO did not cause any change in levels of CDK4 mRNA or protein, whereas etoposide or AraC treatment did diminish CDK4 protein. Enzyme linked immunosorbent assay for pRB and its phosphorylation, which reflects CDK4 activity, revealed that treatment with DFO did not change the amount of pRB or the phosphorylation status. Results of this investigation show that the mechanism of G1 accumulation induced by DFO involves a p53-independent pathway and that expression of p21 protein may be regulated posttranscriptionally.
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PMID:G1 accumulation caused by iron deprivation with deferoxamine does not accompany change of pRB status in ML-1 cells. 926 54

The p53 tumour-suppressor gene is important in the regulation of cell growth and apoptosis, and loss of functional wild-type activity may be associated with tumour formation and resistance to therapy. Differentiation of functionally normal wild-type protein from mutant or abnormal protein remains difficult using either immunohistochemical assays or mutational DNA sequencing. p21(WAF1/CIP1) (p21) is induced by wild type p53 and plays an important role in promoting cell cycle arrest. To test the hypothesis that p21 protein expression may act as a downstream marker of tumours from patients with locally advanced breast cancer before treatment with doxorubicin, pretreatment p53 status had been characterized in 63 tumours by p53 protein immunostaining and DNA mutational analysis. There was a significant association between immunostaining for p53 and the presence of p53 mutations (P = 0.01). Of 56 patients available for determination of p21, 31 (55%) expressed p21 protein. Twenty-eight out of 31 patients (90%) positive for p21 had low negative p53 protein expression, whereas only 3 of 13 patients (23%) with high p53 expressed p21 (P = 0.009). No association was seen between p21 protein expression and p53 mutations (P = 0.24). The combination of p53 and p21 immunostaining results improved the specificity of the immunostaining but at a cost of significant reduction in sensitivity. Immunohistochemical assessment of p21 protein expression is inversely associated with abnormal p53 protein in human breast cancer. The detection of p21 protein expression in combination with p53 protein expression did not improve the ability of immunohistochemistry (IHC) to differentiate between normal and mutant p53 protein.
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PMID:Absence of p21 expression is associated with abnormal p53 in human breast carcinomas. 927 25

We evaluated the effects of various hematopoietic growth factors (HGFs) on the prevention of apoptosis in blasts from 19 patients with acute myeloblastic leukemia (AML) by assessing DNA ladder formation. After incubation without HGF, apoptosis was noted in all but two patients. HGFs prevented, did not affect, or enhanced apoptosis in 39 (60%), 14 (22%), or 12 (18%) of 65 suspension cultures, respectively. HGFs that prevented apoptosis also stimulated and/or synergized blast colony formation in 35 of 39 corresponding methylcellulose cultures. HGFs that alone stimulated colony formation also prevented apoptosis in all but two of 28 corresponding suspension cultures. In contrast, HGFs that did not prevent apoptosis also failed to stimulate growth in 17 of 26 corresponding methylcellulose cultures. HGFs that enhanced apoptosis alone never stimulated colony formation. After incubation, we noted enhanced c-fos and cjun genes as well as induction of p21 protein. An appropriate dose of HGF elevated c-fos, reduced c-jun and p21, induced G1/S transition, and inhibited apoptosis. In two patients, apoptosis was not induced after incubation. Cells not treated with HGF expressed no c-fos, c-jun, or c-myc, and remained in G0/G1. Taken together, our results support the conclusion that not only c-fos, cjun, and c-myc, but also p53 and p21 are required for blast apoptosis. HGF differentially prevents apoptosis and induces mitosis, and both events seem to be integral to the self-renewal of AML clonogenic cells.
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PMID:Differential regulation by hematopoietic growth factors of apoptosis and mitosis in acute myeloblastic leukemia cells. 929 1

The cyclin-dependent kinase, proliferating cell nuclear antigen, and stress-activated protein kinase/c-jun NH2 terminal kinase inhibitor p21WAF1/CIP1 can induce G1 arrest, and its expression coincides with the cessation of replication in many systems. We examined expression of p21 during the early stages of carbon tetrachloride intoxication in the mouse liver and observed a dramatic increase in p21 RNA levels between 4 and 8 h after administration. p21 expression, visualized by in situ hybridization, is induced in pericentral hepatocytes before carbon tetrachloride-induced necrosis. Examination of c-fos and c-myc expression patterns confirm that these immediate-early genes are induced in similar regions of the mouse liver. p21 induction is not dependent on p53; we observed similar levels and localization of p21 in wild-type and p53 null animals. Immunohistochemical localization of p21 and CCAAT/enhancer-binding protein expression shows that p21 protein accumulation is limited to a subset of CCAAT/enhancer-binding protein-positive hepatocytes. A second peak of periportal and intermediate zone-specific p21 gene expression, appearing 1-2 days after injection, is also p53 independent and may represent cell cycle checkpoints or postmitotic growth arrest. Sporadic p21 expression was also detected in pairs of hepatocytes distributed throughout the liver acini in healthy animals. Together, these data suggest several roles for p21 in the liver in response to toxicity, regeneration, and growth inhibition.
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PMID:p53-independent induction of p21WAF1/CIP1 expression in pericentral hepatocytes following carbon tetrachloride intoxication. 930 Jan 78

The bcl-2 protein is found to be over-expressed in many types of human tumours and is a potent inhibitor of apoptosis. The exact mechanism by which bcl-2 prevents apoptosis and exercises its oncogenic effect is still unclear. Other studies on cell lines have reported that bcl-2 over-expression is related to suppression of p21 (WAF1/CIP). We have investigated the relationship between bcl-2 protein over-expression and expression of the p21 protein in a series of human breast carcinomas. Selected tumour samples from 100 breast-cancer patients (38 with abnormal p53 status, scored as protein accumulation and/or mutation, and 62 without detectable p53 alterations), were immunostained for bcl-2 protein, the p21 protein and the oestrogen-receptor (ER) protein. A highly significant association was found between reduced p21-protein expression and over-expression of bcl-2 in tumours with no detectable p53 alterations (p < 0.001). A significant association was seen between ER immunoreactivity and expression of the bcl-2 protein, as well as between bcl-2 protein expression and tumours of the higher differentiation grade (grade-2 tumours). No association was seen between bcl-2 over-expression and the presence of metastases. Our findings indicate that down-regulation of p21 may be a result of up-regulation of bcl-2 independent of p53.
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PMID:Interaction between bcl-2 and p21 (WAF1/CIP1) in breast carcinomas with wild-type p53. 933 7

The proliferation of most cells is strictly dependent on cell-matrix interactions, a phenomenon called anchorage dependence. Because tumor cells often are independent of this regulation, it is important to characterize the molecular pathways that control cellular proliferation after detachment of cells from their matrix. In this report, we investigated a possible role of p53 and one of its target genes, p21(waf1/cip1), as components of anchorage-dependent cell growth control. We found that p53 protein is rapidly activated upon the disruption of cellular attachment. This led to p21 transcriptional activation via two p53-binding sites in its promoter. Elevated p21 protein levels blocked transcription and activity of the cell cycle-regulator cyclin A, and cells became arrested in G1 of the cell cycle. Under the same conditions, fibroblasts from p53 knock-out mice did not activate p21 and did not down-regulate cyclin A expression but rather induced another cell cycle inhibitor, p27. Thus, our results characterize a chain of events, starting from the activation of p53 and proceeding via p21 to cyclin A, that is activated in response to the loss of cellular adherence. This p53-regulated pathway may constitute one of a few redundant systems to ensure proper cell control in multicellular organisms.
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PMID:Activation of p53-p21waf1 pathway in response to disruption of cell-matrix interactions. 936 Sep 84

The p21 protein inhibits the activity of cyclin-Cdk complexes and suppresses cell cycle progression. Wild type p53 can induce p21, but mutated p53 cannot. Previous studies have demonstrated that mutation of p53 is absent in neuroblastoma (NB). These reports prompted us to examine whether p53 induced p21 in NB. We examined the expression of p21 and p53 mRNA in eight NB, two Ewing's sarcoma (ES) and two primitive neuroectodermal tumor (PNET) cell lines by Northern blot analysis, and sequenced p53 cDNA of these cells. Although p53 mRNA was detected in all analyzed cell lines by Northern blot analysis, p21 mRNA was detected in six NB but not in two NB, two ES and two PNET cell lines. We detected the point mutation of p53 at codon 273 (CGT to TGT) in one NB and two ES cell lines. The non-transforming substitution at codon 72 (CCC to CGC) was detected in all analyzed cell lines. One PNET cell line had a large deletion of p53 cDNA. These results showed that p21 mRNA was usually expressed in NB but not in ES and PNET. This may suggest that the down stream of the p53 signal transduction pathway in NB is different from that of the closely related tumors of ES and PNET.
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PMID:p21 (WAF1/Cip1/Sdi1/Pic1) mRNA is expressed in neuroblastoma cell lines but not in Ewing's sarcoma and primitive neuroectodermal tumor cell lines. 936 58

Mimosine (MIM) and aphidicolin (APH) are two agents frequently used in tissue culture-based experiments to achieve cell synchronization at late G1 and S phases. Following MIM or APH treatment of human cancer cell lines, a reversible growth arrest in late G1 and S phases of the cell cycle was correlated with moderate increases in p53 and p21 protein levels. Both p53-dependent and -independent increases in p21 were observed following treatment with either agent. However, a striking increase in p21 protein levels and a continuous elevation in both p53 and p21 protein levels were observed over 48 h after cells re-entered the cell cycle following the chemically-induced synchronization. In addition, the increase in p21 protein levels typically seen following treatment of cells with DNA damaging agents, was enhanced when cells were treated with genotoxic agents following MIM or APH synchronization. These findings suggest that caution should be exercised when interpreting results from experiments using cell synchronization agents, in particular, studies designed to investigate p53- and p21-regulatory pathways.
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PMID:Cell cycle re-entry following chemically-induced cell cycle synchronization leads to elevated p53 and p21 protein levels. 940 Oct 2

The p21 protein inhibits cyclin-dependent kinases and mediates cell-cycle arrest and cell differentiation. It is induced by wild-type p53, but not by mutant p53. This study of 75 patients with endometrial carcinoma investigates the relationship between p21 expression and the functional status of p53, and the usefulness of p21 as a prognostic marker. Correlations were determined between p21 immunoreactivity, p53 overexpression as examined by immunohistochemistry, p53 DNA mutations as examined by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) analysis, and clinicopathological features, including the clinical outcome. Immunoreactivity for p21 and p53 mutations were detected in 47 (62.7 per cent), 37 (49 per cent), and 23 (31 per cent) patients, respectively. There were no significant correlations between the presence or absence of p21 immunoreactivity and p53 overexpression and DNA mutations. Survival curves revealed that patients with p53 overexpression tended to have a poorer prognosis than those without p53 overexpression (P = 0.104), that patients with p53 mutations had a significantly worse prognosis than those without mutations (P = 0.035), and that patients with p21 expression tended to have a better prognosis than those without p21 expression (P = 0.074). Immunohistochemical analysis of p21 was not useful for evaluating the functional status of p53 in patients with endometrial carcinoma. Both p21 expression and p53 abnormalities were considered as prognostic indicators in patients with endometrioid endometrial carcinoma.
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PMID:Correlations between p21 expression and clinicopathological findings, p53 gene and protein alterations, and survival in patients with endometrial carcinoma. 942 88


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