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)

Ninety-four cases of early abortion have been studied. Five histological groups of lesion have been identified by routine histological techniques on abortion materials, group I corresponding to partial hydatidiform mole. Cytogenetic analyses have revealed chromosome anomalies in near 50% of cases with a prevalence of triploidies followed by trisomies and monosomies. Normal histological findings are more often associated with normal karyotypes and group I with abnormal karyotypes but a specific correlation between histological pattern and cytogenetic anomalies is lacking. Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta-hCG, hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific chromosome anomalies. They have only allowed a better definition of histological groups. A simple histological evaluation, although extended to immunohistochemical reaction may not substitute the cytogenetic analyses, not even for purposes of preselection.
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PMID:[Correlation of the histological and cytogenetic pictures in placental tissue from early abortion. Does immunohistochemistry have a role?]. 900 96

The carcinogenic and metastatic processes are thought to consist of a sequence of steps, and animal models featuring highly metastatic lesions are clearly necessary to allow analysis of the whole process of transformation from preneoplastic changes to high grade metastatic tumors, and to access effectiveness of therapeutic treatments of advanced cancers in vivo. The purpose of the present study was to establish a model and to screen for reported genetic alterations in induced lesions. In the present study, it was confirmed that lung metastasis of hepatocellular carcinomas (HCCs) induced in male F344 rats by N-nitrosomorpholine (NNM), given in the drinking water at a dose of 120 ppm for 24 weeks, was significantly enhanced by additional carcinogenic pretreatments and that a single i.p. injection of 100 mg/kg body weight N-diethylnitrosamine (DEN) alone was sufficient for that purpose. Molecular biological analyses of the induced lesions revealed point mutations in the p53 gene in 60.9% of HCCs, and elevated expression of mRNAs for p53, c-myc, c-fos, TGF-alpha, TGF-beta1, alpha-fetoprotein, GST-P, and GGT, and decreased mRNA expression of EGF and EGFR in HCCs when compared to controls. No obvious association of gene alterations with metastatic potential of primary tumors was found except for an increase in the incidence of p53 mutations. Since the process of metastasis is thought to be sequential and selective, further comparative analysis of metastatic and primary lesions should clarify the mechanisms involved in the multi-step process of metastasis.
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PMID:Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes. 902 67

Adrenocortical carcinoma (ACC) is a rare neoplasm with a poor prognosis. Prognostic factors are needed to identify patients who should be treated aggressively and those for which a less aggressive approach is warranted. As a result of advances within the field of immunohistochemistry, investigations of Ki-67, PCNA, IGF, EGF-r and p53 were performed in 17 ACC. The aim of this study was to clarify the role of Ki-67, PCNA, EGF-r, IGF and p53 in correlation to tumour behaviour and outcome. This retrospective study includes 16 patients, 10 women and 6 men, with a median age of 46 years. Nine tumours were hormonally functioning and 7 were non-functioning. The results obtained revealed that all tumours expressed PCNA and Ki-67 with median values of 59% and 14%, respectively, while p53 was negative in 88%, IGF negative in 82% and EGF-r positive in 94% of the tumours. No correlation was found between p53, IGF, EGF-r and survival rate. There was no interdependence between PCNA and Ki-67, or between PCNA, Ki-67 and the survival rate.
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PMID:Biological characteristics of adrenocortical carcinoma: a study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas. 913 90

Primary non-small cell lung cancer samples were examined for the expression of p53, transforming growth factor alpha (TGF-alpha) and its receptor EGF-R by immunohistochemistry. Accumulation of p53 protein was found in 15 out of 24 carcinomas. Meanwhile, the results of TGF-alpha and p53 expression in 21 carcinomas showed that p53 protein was not detected in 2 out of 2 TGF-alpha negative and 4 out of 5 TGF-alpha low expression cases. However, there was no relationship found between EGF-R and p53 expression in these cases. The results suggest that p53 may have some effects on TGF-alpha expression.
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PMID:[Expression of transforming growth factor alpha and p53 in non-small cell lung cancer by immunohistochemical study]. 920 35

Prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the United States, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. Non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papillomavirus 18 which resulted in the establishment of the RWPE-1 cell line. Cells from the RWPE-1 cell line were further transformed by v-Ki-ras to establish the RWPE-2 cell line. The objectives of this study were to: (1) establish the prostatic epithelial origin and androgen responsiveness of RWPE-1 and RWPE-2 cell lines; (2) examine their response to growth factors; and (3) establish the malignant characteristics of the RWPE-2 cell line. Immunoperoxidase staining showed that both RWPE-1 and RWPE-2 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, but they also coexpress basal cell cytokeratins. These cell lines show growth stimulation and prostate specific antigen (PSA) and androgen receptor (AR) expression in response to the synthetic androgen mibolerone, which establishes their prostatic epithelial origin. Both cell lines also show a dose-dependent growth stimulation by EGF and bFGF and growth inhibition when exposed to TGF-beta, however, the transformed RWPE-2 cells are less responsive. RWPE-1 cells neither grow in agar nor form tumors when injected into nude mice with or without Matrigel. However, RWPE-2 cells form colonies in agar and tumors in nude mice. In the in vitro invasion assay, RWPE-1 cells are not invasive whereas RWPE-2 cells are invasive. Nuclear expression of p53 and Rb proteins was heterogeneous but detectable by immunostaining in both cell lines. The RWPE-1 cells, which show many normal cell characteristics, and the malignant RWPE-2 cells, provide useful cell culture models for studies on prostate growth regulation and carcinogenesis.
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PMID:Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. 921 5

Exogenously introduced wild-type and mutant p53 have recently been reported to enhance the human epidermal growth factor receptor (EGF-R) gene promoter activity in p53-deficient Saos2 osteosarcoma cells. A p53 binding site residing at position -265/-239 in the EGF-R proximal promoter has also been identified. We investigated the p53 regulation of EGF-R core promoter activity in human cell lines with varying endogenour p53 status. Wild-type and mutant p53Ala143 enhanced the EGF-R core promotor activity in cells that were either p53-deficient or contained wild-type or mutant endogenous p53. Upon further characterization of the various deletion fragments of the EGF-R promoter, we identified a wild-type p53 responsive 62 bp region residing at position -167/-105. The -167/-105 segment was responsive only to wild-type p53 but not to mutant p53Ala143 or p53His273. The -167/-105 segment of the EGF-R promotor contains one perfect and several imperfect consensus p53-binding half sites; indeed in gel shift experiments the 62 bp -167/-105 segment as well as the oligonucleotides corresponding to two p53 consensus half-sites within the 62 bp fragment, exhibited binding to p53-containing protein complexes. Thus, we have identified an additional wild-type p53 responsive site in the human EGF-R promoter. This site containing consensus p53-binding sequences resides at position -167/-105 and is proximal to recently identified p53 binding element located at position -265/-239 in the EGF-R promotor.
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PMID:Identification of an additional p53-responsive site in the human epidermal growth factor receptor gene promotor. 928 64

EGF, in pharmacological concentrations, inhibits cell proliferation of the MDA-468 human breast cancer cell line. Previously, we have demonstrated that this was characterized by a reversible cell cycle arrest at the G1-S boundary, concomitant with downregulation of mRNA levels for p53 (a point mutant, p53(273.His)). Since p53(273.His) is regarded as a gain-of-function mutant and acts to enhance cell proliferation, we hypothesized that the G1 arrest induced by EGF might be mediated by p53(273.His). In this study, we report an EGF-dependent altered conformation as indicated by immunofluorescence, while no significant immediate effects of EGF-treatment on p53(273.His) protein levels and synthesis were observed. These experiments demonstrated a decreased PAb 240 (mutant-specific) reactivity of nuclear p53(273.His) in EGF-treated cells, while that of PAb 1620 (wild-type specific) was enhanced. Staining with PAb 1801 (pan specific), on the other hand, showed little change upon EGF treatment. Further studies indicated a decreased phosphorylation of nuclear p53(273.His) in EGF-treated cells. These EGF-dependent events were detected early enough to be attributed as causative of cell cycle arrest. We suggest that EGF-mediated, phosphorylation-dependent conformational change in nuclear p53(273.His), and in turn altered p53 function, may be responsible for EGF-dependent growth inhibition MDA-468 cells.
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PMID:EGF effects on p53 in MDA-468 human breast cancer cells: implications for G1 arrest. 933 98

Immunohistochemical analysis of curettage material from a placental site trophoblastic tumor (PSTT) revealed a high expression of p53 gene products, of epidermal growth factor receptor (EGF-R) and of Ki-67 (MIB-1) proliferation associated antigen. bcl-2 was not expressed. These results show that in PSTT inactivation/dysregulation of p53 and upregulation of EGF-R and MiB-1 occurs, indicating that these factors are probably involved in tumor genesis and propagation of PSTT. The prognostic significance of the molecular genetic data, however, remains to be established.
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PMID:P53 gene product and EGF-receptor are highly expressed in placental site trophoblastic tumor. 938 38

Characteristics of human hepatoma cell lines with the wild-type p53 were compared with those of human hepatoma cell lines with the mutant-type p53. The p21 protein located downstream of p53 was expressed in cell lines with the wild-type p53 but was not expressed in cell lines with the mutant-type p53. As to other tumor suppressor genes such as p16 and p27, there was no difference in their expression between both types of cell lines. In addition, no marked difference was observed in the activities of CDK2 and CDK4 between cell lines with the wild-type and the mutant-type p53. Phosphorylated Rb protein was detected in all cell lines except the HLE line, indicating that this cell line may have a deletion of and/or a mutation of the Rb gene. These results indicate that abnormalities of tumor suppressor genes other than p53, p16, p27, and Rb may be involved in hepatocarcinogenesis. The population doubling time of the wild-type p53 cells was significantly longer than that of the mutant p53 cells. Neither type of cell line showed a specific chromosome distribution which would indicate karyotype instability. The cell lines expressing the wild-type p53 produced tumors at lower frequency than those with the mutant p53 gene. Although there was no significant difference in effects of TGF-beta 1, EGF, cholera toxin, and db-cAMP on cell growth between the two types of cells, all three cell lines with the wild-type p53 were resistant to cytotoxicity of TNF-alpha, while two of the three with the mutant p53 were very sensitive to its cytotoxic effects.
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PMID:Comparison of cellular characteristics between human hepatoma cell lines with wild-type p53 and those with mutant-type p53 gene. 943 73

A431 cells hyperproduce EGF receptors and possess inactive p53 proteins. It has been suggested that a cyclin-dependent kinase (CDK) inhibitor p21/WAF1 plays a crucial role in the EGF-induced cell-cycle arrest of A431 cells. Here, we investigated the role of WAF1 gene transcription in the EGF-induced cell-cycle arrest by transfecting the 18-mer antisense oligonucleotide which corresponds to the 5' region of WAF1 gene (AS/WAF1). When A431 cells were treated with EGF, a cascade of responses were observed, including immediate hyperphosphorylation of EGF receptor on tyrosine residues, accumulation of WAF1 mRNA and p21/WAF1 protein, dephosphorylation of RB protein which is a substrate of CDK-cyclin, and cell-cycle arrest. In the presence of AS/WAF1, EGF induced the tyrosine-phosphorylation of EGF receptor, but WAF1 mRNA was reduced to a half; accumulation of p21/WAF1 protein and its downstream responses were no longer observed; A431 cells grew continuously. Thus, the transfection of antisense efficiently prevented A431 cells from the EGF-induced arrest. These observations suggest that p21/WAF1 protein is a major effector molecule of the EGF-mediated cell-cycle arrest of A431 cells.
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PMID:Antisense oligonucleotide of WAF1 gene prevents EGF-induced cell-cycle arrest in A431 cells. 948 44


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