Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With a brother and sister, osteosarcoma developed at the age of 11 and 14 respectively. With both there was no previous retinoblastoma or other bone disease with a proclivity to develop osteosarcoma. We discuss possible explanations for familial aggregation of osteosarcoma, citing external or genetic factors. We suggest that it is the retinoblastoma gene RB and the tumor suppressor gene p53 which play an important part in the development of osteosarcoma.
 ...
PMID:[Osteosarcoma in 2 siblings. A case report]. 750 Jun 7

Although recurrent chromosome abnormalities have been identified in several histologic subtypes of sarcomas, no consistent rearrangement has yet been found in osteosarcomas. Cytogenetic analyses of nine cases of osteosarcoma are reported, including seven newly diagnosed tumors and two recurrent tumors. There were seven high-grade osteosarcomas, one periosteal osteosarcoma, and one well-differentiated sarcoma. All tumors were studied in short-term primary culture. Modal number ranged from near diploid to near triploid. Seven tumors had complex karyotypes with multiple structural abnormalities; two had only normal karyotypes. The retinoblastoma gene on chromosome 13 and the TP53 gene on chromosome 17 have been involved in osteosarcoma. Five tumors had loss of a whole copy of chromosome 13, and three of these also had a loss of a whole copy of chromosome 17. However, these losses were observed in the setting of numerous other chromosome losses. Numerous structural abnormalities were observed, many involving additions of unidentified material, unbalanced translocations, or deletions. Structural abnormalities with similar breakpoints involving 6q, 8q, 9q, and 14p were seen in two or three tumors each. When the tumors in this series were added to the 18 published cases, the pericentromeric regions of chromosomes 1, 3, and 14, and segments 6q15-21, 8q24, 9q34, 12p13, 17p13, and 19q13, were found to be involved in five or more structural rearrangements. Molecular analyses of these chromosome regions may yield genes important in the pathogenesis of osteosarcoma.
 ...
PMID:Chromosome analysis of nine osteosarcomas. 751 49

The human homolog of the murine double minute type 2 gene (MDM2) has been cloned and mapped to 12q13-14. The gene presumably functions as a cellular regulator and mediator of TP53 function. Amplification of the MDM2 gene has recently been observed in soft tissue sarcoma and in osteosarcoma. We studied MDM2 amplification in a series of 94 mesenchymal tumors and found 3-20-fold amplification in 20 tumors: in 10 of 49 malignant fibrous histiocytomas (MFH), in 1 of 2 pleomorphic liposarcomas, in 6 of 7 atypical lipomas, and in 3 of 12 typical lipomas. Normal hybridization patterns were detected in all 16 myxoid liposarcomas, in all 3 leiomyosarcomas, and in all 5 leiomyomas studied. The MDM2 amplification correlated with the presence of marker ring chromosomes; of the 10 MFH with MDM2 amplification, 5 had ring chromosomes, compared to 4 of 39 without MDM2 amplification, and all 9 liposomas with MDM2 amplification had ring chromosomes, in 5 of the tumors as the sole karyotypic anomaly. The correlation between ring chromosomes and MDM2 gene amplification indicates that the marker rings of MFH and of atypical lipoma often harbor genetic material derived from chromosome 12.
 ...
PMID:MDM2 gene amplification correlates with ring chromosome in soft tissue tumors. 751 48

Human osteosarcoma SAOS-2 cells, which have a deletion in p53 gene, were transfected with plasmid pMSVneop53 containing human p53 cDNA and neomycin-resistance gene. Three clones (SAOS-MC10, SAOS-MC11 and SAOS-MC43) among 60 clones expressed p53 mRNA. No p53 protein was observed in SAOS-MC10, while SAOS-MC11 and SAOS-MC43 produced p53 protein. The molecular weight of p53 protein in SAOS-MC43 was lower than that in SAOS-MC11, SAOS-MC11 and SAOS-MC43 were more sensitive and more resistant, respectively, to ionizing radiation than the parental SAOS-2. We suggest that exogenous p53 protein might be one of the factors determining cellular radiosensitivity.
 ...
PMID:Changes in radiation sensitivity of human osteosarcoma cells after p53 introduction. 755 91

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.
 ...
PMID:Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines. 757 9

Genetic changes found in human osteogenic sarcoma cells, including loss of the p53 and Rb tumor suppressor elements and overexpression of the cyclin G1 (CYCG1) proto-oncogene, suggest the potential of gene transfer as a treatment for metastatic disease. In this study, we examined the effects of antisense cyclin G1, in comparison with antisense cyclin D1 (CYCD1) and enforced expression of the universal cyclin-dependent kinase inhibitor p21WAF1/CIP1 on the proliferation of human MG-63 osteosarcoma cells. Retroviral vectors bearing antisense CYCG1 as well as antisense CYCD1 and WAF1/CIP1 (in sense orientation) driven by the Moloney murine leukemia virus long terminal repeat promoter inhibited the growth and/or survival of transduced MG-63 cells in 2-7 day cultures. This represents the first demonstration that cyclin G1 is essential for the survival and/or growth of human osteosarcoma cells. Cytostatic and cytopathic effects were accompanied by a significant increase in the incidence of apoptosis, as determined by immunocytochemical analysis of DNA fragmentation. Furthermore, transduction of MG-63 cells with a retroviral vector bearing the suicide gene, herpes simplex thymidine kinase (HStk), induced cell death on treatment with ganciclovir, exhibiting pronounced bystander effects. Taken together, the data affirm the feasibility of modulating inducible cell cycle control enzymes as a potential gene therapy approach in the clinical management of osteogenic sarcoma.
 ...
PMID:Retroviral vector-mediated gene transfer of antisense cyclin G1 (CYCG1) inhibits proliferation of human osteogenic sarcoma cells. 758 20

The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in a subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing WT1 under an inducible tetracycline-regulated promoter. Induction of WT1 resulted in programmed cell death. This effect, which was differentially mediated by the alternative splicing variants of WT1, was independent of p53. WT1-mediated apoptosis was associated with reduced synthesis of the epidermal growth factor receptor (EGFR), but not of other postulated WT1-target genes, and it was abrogated by constitutive expression of EGFR. WT1 repressed transcription from the EGFR promoter, binding to two TC-rich repeat sequences. In the developing kidney, EGFR expression in renal precursor cells declined with the onset of WT1 expression. Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles.
 ...
PMID:WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. 758 96

A mutation in the tumor suppressor p53 gene resulting in an Arg-->Ser substitution in position 249 is found frequently in human hepatocellular carcinomas associated with hepatitis B infection and with aflatoxin exposure. To determine the significance of this mutation in an in vivo experimental model using transgenic mice, we introduced a two-nucleotide change in the mouse p53 gene at amino-acid position 246, which is equivalent to position 249 in human p53, by the recombinant polymerase chain reaction mismatched primer method. This p53 mutation resulted in the same change, an Arg-->Ser substitution, as in the human p53 gene at position 249. We now report that the protein product of this mutant mouse p53ser246 had properties similar to those of the wild-type protein when tested by binding to (i) monoclonal antibodies PAb246 and PAb240, ii) simian virus 40 large T antigen, and (iii) heat-shock protein. However, it had mutant-type transforming properties when tested for colony formation with an osteosarcoma cell line. It was not active, as is wild-type p53, in transcription activation of the muscle creatine kinase promoter. These properties are the same as those found in the p53trp248 product of the p53 mutation associated with the Li-Fraumeni syndrome. Although less is known about the human p53ser249 product associated with hepatocellular carcinoma, the mutant murine p53ser246 protein shares the known properties of the human gene product.
 ...
PMID:Characterization of a murine p53ser246 mutant equivalent to the human p53ser249 associated with hepatocellular carcinoma and aflatoxin exposure. 760 78

We demonstrated a germline p53 replication error in two generations of a Li-Fraumeni family affected with liposarcoma, adrenocortical carcinoma, and osteosarcoma. The trinucleotide repeat mutation changed 5'-AGT GTG GTG GTG-3' at codons 215-218 to 5'-AGT TGG TTG GTG GTG-3'. The predicted protein would be elongated by one amino acid (val216-->trp leu) without a change in charge. Detection of p53 in the adrenal tumor by immunostaining suggested that the mutant protein was expressed. Persistence of the mutation in the germline may suggest a defect in DNA repair in the family member first affected. This is the first report where germline transmission of replication-damaged p53 trinucleotide repeats is associated with the Li-Fraumeni syndrome.
 ...
PMID:Complex replication error causes p53 mutation in a Li-Fraumeni family. 761 54

Recombinant adenovirus Ad5CMV-p53 induced a strong cytocidal effect in Saos-LM2 cells. This cell line, derived from human osteosarcoma Saos-2 cells, has a homozygous deletion of the p53 gene. By using immunocytochemical and Western blot analyses, we demonstrated that Ad5CMV-p53 effectively infected Saos-LM2 cells at multiplicities of infection of 10 to 50 plaque-forming units/cell and mediated a high-level expression of the exogenous wild-type p53 protein in the cells. Growth of the infected cells was greatly suppressed whereas that of mock- or control virus-infected cells was not. Because wild-type p53 induces apoptosis in certain types of cells, we studied DNA fragmentation in situ in the Ad5CMV-p53-infected Saos-LM2 cells by terminal deoxynucleotidyl transferase assays, which yielded positive nuclear staining. Further analysis of the Ad5CMV-p53-infected Saos-LM2 cells by light and electron microscopy demonstrated that the cells underwent the characteristic morphological changes of apoptosis such as plasma-membrane blebbing, nuclear condensation, and fragmentation. These changes were not observed in mock- or control virus-infected cells. Our results on Saos-LM2 cells indicate that apoptosis induced by Ad5CMV-p53 may be one of the mechanisms underlying the cytocidal effect of Ad5CMV-p53.
 ...
PMID:Apoptosis induced in human osteosarcoma cells is one of the mechanisms for the cytocidal effect of Ad5CMV-p53. 762 Dec 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>