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 tumor suppressor protein p53 is a major cell cycle control factor, and mutations in p53 are the most common genetic lesion found in human tumors, resulting in loss of function and contributing to malignant transformation. This report reviews several studies which show that p53 protein appears as at least eleven isoforms having the same amino acid backbone but varying in charge by level of phosphorylation. All isoforms are derived from a single locus, which indicates that p53 activity is modulated by post-translational modification. In addition, mutant p53 forms hetero-oligomers with two families of proteins: HSP70 and a 90 kDa group similar to HSP90. Cytoplasmic complexes are most likely formed to protect p53 from proteolysis and are probably involved in translocation of activated p53 from the cytoplasm to the nucleus for transactivation of other cell cycle control genes.
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PMID:Tumor suppressor p53 gene forms multiple isoforms: evidence for single locus origin and cytoplasmic complex formation with heat shock proteins. 898 9

Curcumin (diferuloyl methane) is the major active yellow pigment of turmeric and curry. Studies in recent years have indicated that curcumin is a potent inhibitor of the initiation and promotion of chemical carcinogen-induced skin carcinogenesis in mice. When COLO205 colorectal carcinoma cells were treated with curcumin (60 microM), the appearance of apoptotic DNA ladders was delayed about 5 h, and G1 arrest was detected. Further analysis of the endonuclease activities in these cells revealed that the activity of Ca(+2)-dependent endonuclease in COLO205 cells was profoundly inhibited and that the extent of inhibition depended on the degree of calcium depletion. The reduction of p53 gene expression was accompanied by the induction of HSP70 gene expression in the curcumin-treated cells. These findings suggest that curcumin may induce the expression of the HSP70 gene through the initial depletion of intracellular Ca(+2), followed by the suppression of p53 gene function in the target cells.
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PMID:Induction of HSP70 gene expression by modulation of Ca(+2) ion and cellular p53 protein by curcumin in colorectal carcinoma cells. 898 16

A case of carcinosarcoma composed of both adenocarcinoma and sarcomatous elements in the non-trigone region of the urinary bladder is presented. The epithelial element was a well to poorly differentiated adenocarcinoma with focal squamous metaplasia. The sarcomatous elements disclosed spindle cell sarcoma with focal epithelioid pattern and myxoid change in the stroma, together with chondrosarcomatous and rhabdomyosarcomatous elements. By immunohistochemical examination, not only the carcinoma element but also the sarcomatous elements showed a positive immunoreaction for cytokeratin (CK), epithelial membrane antigen (EMA) and carcinoembryonic antigen. Some population of sarcomatous elements expressed smooth muscle actin and muscle specific actin (MSA) and a limited portion of epithelioid area showed a positive immunoreaction for desmin, MSA and myoglobin, indicating leiomyosarcomatous and rhabdomyosarcomatous differentiation, respectively. Unexpectedly, tumor cells in the chondrosarcomatous element revealed a simultaneous positivity of CK and EMA as well as S-100 protein. Both epithelial and sarcomatous elements showed an intensive positive immunoreaction for p53 and heat shock protein (HSP) 70. However, HSP27 and HSP60 were detected in most epithelial elements and only in a small number of tumor cells in the sarcomatous area. These findings indicate that sarcomatous elements, including heterologous elements, may derive from epithelial elements with partial or complete loss of epithelial features, and different factors other than p53 and HSP70 may associate with the morphological alteration of carcinoma.
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PMID:Carcinosarcoma of the urinary bladder: expression of epithelial markers and different expression of heat shock proteins between epithelial and sarcomatous elements. 908 35

Mutations within conserved regions of the tumor suppressor protein, p53, result in oncogenic forms of the protein with altered tertiary structures. In most cases, the mutant p53 proteins are selectively recognized and bound by members of the HSP70 family of molecular chaperones, but the binding site(s) in p53 for these chaperones have not been clearly defined. We have screened a library of overlapping biotinylated peptides, spanning the entire human p53 sequence, for binding to the HSP70 proteins, Hsc70 and DnaK. We show that most of the high affinity binding sites for these proteins map to secondary structure elements, particularly beta-strands, in the hydrophobic core of the central DNA binding domain, where the majority of oncogenic p53 mutations are found. Although peptides corresponding to the C-terminal region of p53 also contain potential binding sites, p53 proteins with C-terminal deletions are capable of binding to Hsc70, indicating that this region is not required for complex formation. We propose that mutations in the p53 protein alter the tertiary structure of the central DNA binding domain, thus exposing high affinity HSP70 binding sites that are cryptic in the wild-type molecule.
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PMID:HSP70 binding sites in the tumor suppressor protein p53. 923 49

Serial analysis of gene expression (SAGE) allows for a quantitative, representative, and comprehensive profile of gene expression. We have utilized SAGE technology to contrast the differential gene expression profile in rat embryo fibroblast cells producing temperature-sensitive p53 tumor suppressor protein at permissive or non-permissive temperatures. Analysis of approximately 15,000 genes revealed that the expression of 14 genes (P < 0.001, > or = 0.03% abundance) was dependent on functional p53 protein, whereas the expression of three genes was significantly higher in cells producing non-functional p53 protein. Those genes whose expression was increased by functional p53 include RAS, U6 snRNA, cyclin G, EGR-1, and several novel genes. The expression of actin, tubulin, and HSP70 genes was elevated at the non-permissive temperature for p53 function. Interestingly, the expression of several genes was dependent on a non-temperature-sensitive mutant p53 suggesting altered transcription profiles dependent on specific p53 mutant proteins. These results demonstrate the utility of SAGE for rapidly and reproducibly evaluating global transcriptional responses within different cell populations.
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PMID:SAGE transcript profiles for p53-dependent growth regulation. 928 62

In contrast to intrinsic drug resistance, induced multidrug resistance in gastric cancer cells has not been well studied. Therefore, two doxorubicin-resistant cell lines, (SNU-1DOX, SNU-16DOX), were derived in vitro from gastric carcinoma cell lines (SNU-1, SNU-16) respectively, and their characteristics were investigated. These resistances were not associated with overexpression of mdrl, multidrug resistance associated protein 1 (MRP1), pi or liver class of glutathione S transferase (GST pi, GSTL), heat shock protein 70 (HSP70), p53 or transglutaminase C (TGC). Levels of p21WAF1 RNA and topoisomerase II protein were decreased in the SNU-16DOX, but not in SNU-1DOX. However, the subsequent enzyme activity of topoisomerase II in SNU-16DOX was not decreased, but rather increased in SNU-16DOX. Furthermore, both resistant cell lines showed lower uptake and higher efflux of doxorubicin and induced cross-resistance to etoposide and vincristine in addition to doxorubicin, indicating a multi-drug resistance phenotype. In summary, we report two gastric carcinoma cell lines exhibiting induced multidrug resistance phenotype and suggest that mdrl, MRP1, GST, TGC, HSP70 and p53 do not play important roles in induced drug resistance in these cell lines. The role of changes in topoisomerase II activity and/or protein is still inconclusive, and p21WAF1 is associated with induced multidrug resistance in the SNU-16DOX gastric carcinoma cell line.
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PMID:Characteristics of human gastric carcinoma cell lines with induced multidrug resistance. 941 98

The functional significance of alterations in expression of tumour-suppressor gene p53 and 70-kDa heat-shock protein (HSP70) in eliciting p53-specific humoral response in oral-cancer patients is not yet known. In this study, p53 auto-antibodies were analyzed in sera from oral-cancer patients by immunoblotting and results were correlated with clinicopathological features of the patients as well as with the levels of HSP70, p53 and p53-HSP70 complexes in matched patients' tumour tissue, for determining their diagnostic/prognostic significance and relationship to survival. Circulating anti-p53 antibodies were observed in 7 of 30 cancer patients and 3 of 25 patients with pre-malignant lesions. Over-expression of p53 protein in matched oral lesions was observed in 22 of these 30 cancer patients and 14 of 25 patients with dysplastic lesions. No detectable levels of p53 protein or anti-p53 antibodies were observed in normal subjects (15 cases). Elevated levels of HSP70 were observed in 23 of these 30 oral tumours and 17 of 25 dysplastic lesions. All the anti-p53-antibody-seropositive cases showed elevated levels of p53 and HSP70 proteins, as well as formation of p53-HSP70 complexes, in matched dysplastic or malignant lesions, suggesting that these molecular alterations may be early events in oral tumorigenesis and are implicated in eliciting p53-specific humoral immune response in these patients. Anti-p53-antibody-seropositive cases showed poor prognosis and significantly decreased overall disease-free survival in comparison with the seronegative cases. Detection of circulating anti-p53 antibodies may serve as a useful non-invasive marker for identifying oral tumours having poor prognosis.
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PMID:Serum p53 antibodies in patients with oral lesions: correlation with p53/HSP70 complexes. 942 57

1. The effects of quercetin on drug metabolising enzymes and oxygen radicals were studied in human HepG2 cells. 2. Cytotoxicity of quercetin in HepG2 cells was seen at 50 microM and above as evaluated by lactate dehydrogenase (LDH) leakage, neutral red (NR) uptake, and 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction. 3. Quercetin inhibited activity of human cytochrome P-450 towards ethoxycoumarin and ethylresorufin at relatively low substrate concentrations (0.1 microM and above). 4. In comparison to induction by the positive control (beta-naphthoflavone; 1.0 microM), quercetin did not significantly induce the metabolism of ethoxycoumarin or glutathione-S-transferase (GST) protein or activity. 5. Response elements for human CYP1A1, GST lambda a, xenobiotic response element (XRE), fos, HSP70, CRE, p53, NF kappa B and DNA damage (GADD) in HepG2 cells were not activated by quercetin. 6. Quercetin exhibited antioxidant activity in HepG2 cells as evidenced by its ability to inhibit the oxidation of the fluorochrome dichlorofluorescin. 7. The results indicate a range of potential beneficial effects of quercetin with respect to the influence on carcinogen-metabolising enzymes, scavenging of reactive oxygen species and a lack of stress response in HepG2 cells.
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PMID:Effects of quercetin on drug metabolizing enzymes and oxidation of 2',7-dichlorofluorescin in HepG2 cells. 942 83

Twenty-four specimens of squamous cell carcinoma of the tongue were immunostained for heat shock proteins (HSPs) to reveal differences in stainability among normal epithelium, dysplasia and carcinoma and to clarify the prognostic significance of HSPs in comparison with survival period, clinical stage, lymph node metastasis, histological grade, and p53 immunostaining. Normal epithelium was positively stained in the suprabasal layer for HSP60 and HSP70, but was negative for HSP27 and HSP90. Dysplastic lesions were positive for HSP27, HSP70 and HSP90, but stained variously for HSP60. In squamous cell carcinoma, the cytoplasm of suprabasal tumor cells was often positive for HSP27 and HSP90 (18/24, 17/24, respectively). Although HSP immunohistochemistry has revealed changes in HSP expression during tumorigenesis of squamous epithelium of the tongue, there was no correlation between HSP staining and survival period, stage, lymph node metastasis, histological grade or p53 immunostaining.
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PMID:Expression of heat shock proteins in squamous cell carcinoma of the tongue: an immunohistochemical study. 946 30

Heat shock proteins HSP70 and HSP90 are sex steroid receptor-associated proteins, and HSP90 expression has reportedly been correlated with sex steroid receptor status in endometrial carcinomas. HSP70 is also known to associate with several oncogene products such as p53 protein, and expression of HSP70 has been reported to be a prognostic factor in several malignant neoplasms. In endometrial carcinomas, however, little is known about the prognostic significance of these proteins. Therefore, we analyzed the survival of 44 endometrial carcinoma patients treated in our hospital with reference to the immunohistochemical expressions of HSP70 and HSP90, as well as the clinicopathological factors such as age, menstrual status, FIGO stage, histologic grade, p53 protein overexpression, and sex steroid receptor status. The expression of HSP70 was observed in 50% (22 cases), and strong HSP90 expression in 30% (13 cases) of the 44 carcinomas. The patients with HSP70-positive tumors showed significantly poorer survival than the patients with HSP70-negative tumors (p = 0.045), although multivariate analysis did not reveal HSP70 expression to be an independent prognostic factor. In contrast, the strong expression of HSP90 in the tumor was significantly correlated with a favorable prognosis of the patient (p = 0.026). Other prognostic indicators were FIGO stage (p = 0.0086) and the expression of progesterone receptor (p = 0.042). Accordingly, expressions of HSP70 and HSP90 each have different prognostic significance in endometrial carcinoma and may be useful for prediction of patient survival.
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PMID:Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. 982 79


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