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)

Cytogenetic analysis of a cemento-ossifying fibroma from a patient with nonfamilial bilateral multicentric retinoblastoma revealed three reciprocal translocations with the karyotype 46,XY,t(1;18)(q21;q21.3),t(3;10)(p13;q22),t(6;11)(p22;p15). Routine and high-resolution cytogenetic analysis of peripheral blood leukocytes showed an apparently normal, 46,XY chromosome pattern with no deletion of chromosome 13. Molecular analysis demonstrated no gross differences in the retinoblastoma gene or the TP53 gene between constitutional and tumor DNA. This is the first cytogenetic analysis of a cemento-ossifying fibroma and the first report of this tumor in a retinoblastoma patient. The data may be added to the small, but growing literature on cytogenetic aberrations in benign tumors and may lend insight into genes involved in cell proliferation and neoplastic transformation.
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PMID:Cytogenetic abnormalities in an ossifying fibroma from a patient with bilateral retinoblastoma. 137 15

The humoral immune response over time of White Leghorn chickens experimentally infected with Mycoplasma gallisepticum or M. synoviae by an aerosol inoculation or a contact exposure were compared by immunoblotting. The response of chickens infected with M. gallisepticum were similar with respect to proteins recognized and intensity of response, regardless of mode of infection. On the other hand, chickens infected by aerosolization of M. synoviae responded to more proteins and with greater intensity than did M. synoviae contact-exposed birds. Chickens infected with M. gallisepticum responded with antibodies to over 20 proteins, while chickens infected with M. synoviae responded with antibodies to 12 proteins. Field sera from chickens naturally infected on commercial poultry farms with M. gallisepticum or M. synoviae were analyzed by immunoblotting and were found to react with a number of mycoplasma proteins. However, no correlation was seen when comparing intensity of immunoblot staining and hemagglutination-inhibition titer of the field sera. The experimental antisera were used to identify species-specific proteins of M. gallisepticum and M. synoviae. Six immunogenic species-specific proteins of M. gallisepticum with relative molecular masses of 82 (p82), 65-63 (p64), 56 (p56), 35 (p35), 26 (p26), and 24 (p24) kilodaltons (kDa) were identified. Two species-specific proteins of M. synoviae with relative molecular masses of 53 (p53) and 22 (p22) kDa were identified. Additionally, a highly immunogenic 41 (p41) kDa protein of M. synoviae was identified. Species-specific proteins identified in these mycoplasmas and the 41 kDa protein of M. synoviae were purified by preparative SDS-PAGE in amounts sufficient for further characterization and for use in serodiagnostic tests.
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PMID:The humoral immune response of chickens to Mycoplasma gallisepticum and Mycoplasma synoviae studied by immunoblotting. 214 97

Antibody spectra to individual proteins of human immunodeficiency virus (HIV) in 74 seropositive serum samples collected in the USSR and 65 serum samples collected in Britain were studied by immunoblotting techniques. Most of the sera belonged to clinically healthy persons, some of the sera collected in Britain contained specific IgM antibodies. The results were evaluated qualitatively and quantitatively. In the former case the study of samples collected both in the USSR and in Britain yielded similar results which also coincided with the data of literature regarding asymptomatic virus carriers: very high content of antibodies to protein gp41 and sufficiently high content of antibodies to protein p24 were registered in all sera. But the quantitative evaluation of the results of this investigation revealed differences between serum samples collected in these two countries. The main feature of sera collected in the USSR was their noticeably greater reactivity with respect to the products of HIV gene gag: proteins p24, p53 and p22. The explanations of this phenomenon are discussed.
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PMID:[A comparison of the spectra of antibodies to individual proteins of the human immunodeficiency virus in seropositive sera collected in the territories of the USSR and England]. 258 79

The MTS1 gene on chromosome 9p21 encodes the p16 inhibitor of cyclinD/Cdk-4 complexes, and is deleted or mutated in a variety of tumour types. We found allelic deletions of 9p21-p22 in 85% of pancreatic adenocarcinomas. Analysis of MTS1 in pancreatic carcinomas (27 xenografts and 10 cell lines) showed homozygous deletions in 15 (41%) and sequence changes in 14 (38%). These included eight point mutations (four nonsense, two missense and two splice site mutations) and six deletions/insertions, all accompanied by loss of the wild-type allele. Sequencing of MTS1 from primary tumours confirmed the mutations. Coexistent inactivations of both MTS1 and p53 was common and suggests that abnormal regulation of cyclin-dependent kinases may play an important role in the biology of pancreatic carcinoma.
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PMID:Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. 772 12

Adenocarcinoma of the pancreas is currently the fifth leading cause of death in the United States. It remains generally incurable by available treatment modalities. We report here on the characterization of a permanent pancreatic cell line (KCI-MOH1), established as a xenograft in severe combined immune deficient (SCID) mice, from a 74 year-old African American male patient diagnosed with pancreatic cancer. Sections from paraffin-embedded tumors excised from SCID mice revealed typical adenocarcinoma of the pancreas. Karyotypic analysis of cultured cells derived from tumors grown in SCID mice revealed a male karyotype with multiple clonal aberrations: 42, XY, add (3)(p11.2), der(7) t(7;12) (p22;q12), -10, -12, add (14)(p11), -18, add (20)(q13)-22/84, idemx2. Immunostaining of KCI-MOH1 tissues shows strong expression of p53 and p21 proteins. The xenograft model was established by transplanting the KCI-MOH1 cells subcutaneously (s.c.) in SCID mice. When the s.c. tumor was transplanted in vivo to other SCID mice, the success rate was 100%, with a doubling time of 8.5 days. The SCID mouse xenograft model was used to test the efficacy of selected standard chemotherapeutic drugs (taxol, gemcitabine, 5-fluorouracil, and Ara-C) and novel biological agents (Bryostatin 1 and Auristatin-PE). Results show that gemcitabine, Ara-C, and Bryostatin 1 were active against KCI-MOH1. The xenograft described herein can be used as an animal model to facilitate the development of novel therapeutic agents against human pancreatic cancers.
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PMID:Establishment of a human pancreatic tumor xenograft model: potential application for preclinical evaluation of novel therapeutic agents. 943 58

The novel early response gene p22/PRG1 is linked to cell cycle entry and the induction of proliferation in various cell types although its exact function is still unknown. The p22/PRG1 promoter region contains a 20 bp sequence matching the consensus binding motif for the tumor suppressor protein p53. Gel shift assays demonstrated that p53 specifically binds to an oligonucleotide derived from the p53 binding site of the p22/PRG1 promoter. Chloramphenicol acetyltransferase (CAT) reporter gene assays confirmed that this site confers p53-dependent transcriptional activity to the p22/PRG1 promoter. In Hela cells, p22/PRG1 promoter constructs induced CAT expression only when cotransfected with an expression plasmid for wild-type, but not for mutant p53. Similarly, CAT expression was inducible at the permissive (31 degrees C) but not at the non-permissive temperature (39 degrees C) in the rat embryo fibroblast-derived cell line clone-6 that expresses a temperature-sensitive mutant p53. Conversion of this mutant p53 to a functional p53 at the permissive temperature was accompanied by a significant increase of endogenous p22/PRG1 mRNA level in this cell line. Gamma-irradiation of rat splenocytes or doxorubicin-treatment of Hela cells increased p53 levels followed by transcriptional activation of p22/PRG1 and p21/Waf1 in parallel. Our data demonstrate that p22/PRG1 transcription is induced by p53 during p53-dependent cell cycle arrest and apoptosis. Therefore, p22/PRG1 represents a novel target for transcriptional activation by p53.
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PMID:The proliferation-associated early response gene p22/PRG1 is a novel p53 target gene. 962 14

Recent methodological developments allow expression measurement of many genes simultaneously, thereby revealing patterns of gene expression that can be related to phenotype. We hypothesized that through the use of such methods we could identify patterns of gene expression associated with the malignant phenotype in human bronchial epithelial cells (BEC). To test this hypothesis, a recently developed quantitative reverse transcriptase polymerase chain reaction method was used to assess simultaneously expression of 15 genes mechanistically associated with cell-cycle control (c-myc, E2F-1, p21, rb, PCNA, cyclin D2, cyclin D3, cyclin E, cdc2, CDK2, CDK4, mad, max p21, max p22, and p53) in normal cell cultures from five individuals and in nine different malignant BEC lines. Relative to the mean expression levels in cultured normal cell populations, expression of c-myc, E2F-1, PCNA, cyclin E, and CDK4 messenger RNA (mRNA) were significantly increased and expression of p21 and p53 mRNA were significantly decreased in one or two, but not all three subtypes (squamous, adenocarcinoma and small cell) of carcinoma cell lines evaluated. No single cell-cycle control gene discriminated all three subtypes from normal cell populations. In contrast, the gene expression index c-myc x E2F-1/p21 separated all carcinoma cell lines from all normal cell populations initially evaluated. This malignancy index was validated in an additional three cultured normal BEC and three carcinoma cell lines, as well as three pairs of matched primary normal bronchial epithelial and primary bronchogenic carcinoma samples, and three pairs of matched primary normal lung parenchyma and primary bronchogenic carcinoma tissue. Again, the c-myc x E2F-1/ p21 index successfully discriminated all cultured and primary normal from malignant samples and thereby had a predictive value of 1 (no false positives and no false negatives). We hypothesize that because of functional mutations in cell-cycle regulatory genes (e.g., p53 and/or rb), cells lose the ability to maintain a pattern of gene expression mechanistically associated with normal, division-limited homeostatic equilibrium. Because the c-myc x E2F-1/p21 gene expression index has high specificity for malignant tissue, it will allow confirmation that there is a significant amount of tumor tissue present in small (e.g., fine-needle) biopsy specimens prior to evaluating them for expression of other genes, such as those involved in chemoresistance or radioresistance. In addition, the goal of most gene therapy efforts is to alter levels of gene expression quantitatively. This index and others derived in a similar manner may better define potential gene therapy targets as well as response of targeted genes to therapy.
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PMID:The gene expression index c-myc x E2F-1/p21 is highly predictive of malignant phenotype in human bronchial epithelial cells. 965 Nov 76

We describe functional binding sites for the tumor suppressor p53 and for NFkappaB residing in the promoter of the novel human early response gene p22/PRG1 (IEX-1/DIF-2). Gel shift and supershift assays demonstrate binding of p53 and NFkappaB to their corresponding sites in vitro. CAT-reporter gene assays show transactivation of the human p22/PRG1 promoter by p53 in Hep3B cells stably transfected with a temperature-sensitive mutant p53, but not in p53-deficient Hep3B cells. TNF alpha induced NFkappaB dependent transactivation was shown in HepG2 cells or in 818-4 pancreatic cancer cells. These data imply that human p22/PRG1 is a target gene for p53 and NFkappaB involved in growth regulation and stress response.
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PMID:The promoter of human p22/PACAP response gene 1 (PRG1) contains functional binding sites for the p53 tumor suppressor and for NFkappaB. 978 66

In this study we describe a novel putative p53-responsive gene, designated p22/PACAP response gene 1 (PRG1), recently identified as a proliferation-associated early-response gene in rats. By means of electrophoretic mobility shift assay and CAT-reporter gene assay, we could demonstrate that the p53 binding site residing in the promoter of p22/PRG1 is functional in vitro. Furthermore, in clone 6 cells expression of p22/PRG1 is induced in parallel to p21/Waf1 under conditions permitting mutant p53 to adopt wild-type configuration. An increase of p22/PRG1 transcription was also observed in gamma-irradiated rat splenocytes, which undergo p53-dependent apoptosis. Our findings demonstrate that p22/PRG1 fulfills all essential criteria as a p53 target gene and might be implicated in p53-dependent apoptosis.
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PMID:p22/PACAP response gene 1 (PRG1): a putative target gene for the tumor suppressor p53. 992 93

We report a rare large B-cell non-Hodgkin's lymphoma having a characteristic near-triploid cell population with add(17)(p22) and t(14;18)(q32;q21) translocation. We also established and characterized a new cell line (TK cell) derived from the present lymphoma. A codon 180 mutation (GAG --> GAT) in the p53 gene was detected. t(14;18)(q32;q21) was revealed juxtaposition of the bcl-2 and JH genes. Immunoprecipitation analyses of p53 and bcl-2 revealed that abnormality of the p53 protein and aberrant bcl-2 expression, which may protect cells from apoptosis, may be critical to the development of leukaemogenesis exhibiting near-triploid chromosomes.
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PMID:Establishment of a near-triploid human B-cell lymphoma cell line with t(14;18) and a p53 gene point mutation. 1035 43


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