Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 gene has been found to be mutated in many different kinds of human cancers. In a previous study, expression of exogenous wild-type p53 in human osteosarcoma cells by retrovirus-mediated gene transfer resulted in marked enlargement of cell size, reduced growth rate in culture and loss of tumorigenicity in nude mice. Here we examine the effects of expression of wild-type or mutated p53 on human peripheral neuroepithelioma (PNET) A673 cells; these cells contained apparently normal alleles of the p53 gene but did not express a detectable quantity of p53 protein. Various characteristics of the p53-expressing cells were examined including morphology, growth rate, soft-agar colony formation, and tumorigenicity in nude mice. In contrast to osteosarcoma Saos-2 cells, expression of wild-type or mutant p53 protein in A673 cells had no effect on morphology or growth characteristics. However, clones expressing wild-type p53 protein had reduced ability to form colonies in soft agar and tumors in nude mice. To substantiate the genotype of wild-type p53-expressing cells, the proviral p53-encoding DNA of one cell clone was amplified by the polymerase chain reaction and sequenced. We concluded that expression of a single allele of the wild-type p53 gene was sufficient to suppress PNET A673 tumorigenicity but had no detectable effect on growth rate in culture.
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PMID:Expression of wild-type p53 in human A673 cells suppresses tumorigenicity but not growth rate. 192 5

Previously, we have shown that the chicken anemia virus-derived VP3 ("apoptin") protein induces apoptosis in chicken mononuclear cells. Here, we report that apoptin also induces apoptosis in human osteosarcoma cells, regardless of whether they expressed wild-type, mutant p53, or no p53 at all. Moreover, the nuclear location of apoptin appears to be important for its optimal induction of apoptosis. The fact that apoptin can induce p53-independent apoptosis in human tumor cells makes apoptin a potential candidate for treatment of frequently occurring types of cancer cells that do not contain functional p53.
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PMID:Apoptin, a protein derived from chicken anemia virus, induces p53-independent apoptosis in human osteosarcoma cells. 783 13

The p53 gene undergoes rearrangement in a high percentage of osteosarcomas, resulting in loss of its expression. A p53-null murine osteosarcoma cell line F6 was transfected with either a wild-type or a mutant p53 gene. Stably transfected cell lines were obtained, and their differentiation capabilities were compared in vitro with the parental cell line. Alkaline phosphatase and osteocalcin expression were measured as early and late differentiation markers, respectively. Induction of alkaline phosphatase expression was not affected by the presence of either p53 gene, whereas osteocalcin expression was seen in cells containing the wild-type p53 gene but not in the parental p53-null or mutant-expressing cell lines. That the induction of osteocalcin was intrinsically dependent on the presence of wild-type p53 was also indicated by the use of a temperature-sensitive Val 135 p53 mutant at 32 degrees C; predominant expression of p53 in the wild-type conformation resulted in osteocalcin expression. While the wild-type p53 gene could suppress tumor formation in vivo, the tumors expressing the mutant p53 gene grew two to three times as large as the tumors that did not express p53. Therefore, the absence of end-point differentiation in bone due to p53 rearrangements may contribute to the maintenance of the tumorigenic phenotype in osteosarcomas.
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PMID:Dependence of induction of osteocalcin gene expression on the presence of wild-type p53 in a murine osteosarcoma cell line. 828 Mar 78

Alterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewing's sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giant-cell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.
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PMID:Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone. 841 91

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

We used a yeast functional assay (functional analysis of separated alleles in yeast: FASAY) to determine the p53 gene status of human cell lines maintained in our laboratory. This assay enables the researcher to score wild-type p53 expression on the basis of the ability of expressed p53 to transactivate the reporter gene HIS 3 via the p53-responsive GAL 1 promoter in Saccharomyces cerevisiae. The cell lines examined were ten hepatoma, two hepatoblastoma, three in vitro immortalized fibroblast, two osteosarcoma, a chondrosarcoma, an ovarian teratocarcinoma and a colon cancer cell line. Out of 20 cell lines, 11 cell lines had mutations in both alleles of the p53 gene, and another 8 cell lines had no mutation in the p53 gene. Thus, 55% of the cell lines examined had mutations in the p53. Interestingly, PA-1 cells had both the normal and the mutant p53 alleles, showing that FASAY is a useful method for detecting the wild-type and mutated p53 genes simultaneously. As for the three liver cell lines harboring HBsAg, there was no relationship between their p53 gene status and the presence of HBsAg. Two cell lines were normal for p53 status, while the other had a mutation of the p53 gene.
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PMID:Yeast functional assay of the p53 gene status in human cell lines maintained in our laboratory. 935 23

Induction of WAF1 expression was investigated in human glioblastoma cell lines differing in p53 gene statuses after cold shock treatment. Accumulation of both wild-type (wt) and mutant p53 (mp53) was induced by cold shock at 4 degrees C for 60 min, however, WAF1 accumulation was induced by cold shock in A-172 cells carrying the wtp53 but not in T98G cells carrying the mp53. Inactivation of wtp53 by a dominant negative p53 mutant (p53Trp248) abolished cold shock-induced WAF1 expression in A-172 transfectant cells. Furthermore, no WAF1 expression was induced by cold shock in p53-deficient human osteosarcoma Saos-2 cells. Northern blot analysis showed that the WAF1 but not p53 gene was activated by cold shock only in A-172 cells. These findings suggest that WAF1 expression is cold shock-inducible in human glioblastoma cells, and that this induction may be due to signal transduction mediated by p53 in response to non-genotoxic stress, cold shock.
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PMID:p53-dependent induction of WAF1 by cold shock in human glioblastoma cells. 952 49

The induction of WAF1 gene expression after the treatment with the anticancer agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU; nimustine hydrochloride) was studied in two human glioblastoma cell lines: U-87MG, which bears the wild-type p53 gene, and T98G, which bears the mutant p53 gene. A marked accumulation of WAF1 was observed 3 h after ACNU treatment in both cell lines. The induction of WAF1 mRNA by ACNU was detected by northern blot analysis in these cells. Binding activity of p53 to a p53 consensus sequence increased after treatment in U-87MG cells but not in T98G cells. The existence of a p53-independent WAF1 induction pathway was supported by the apparent accumulation of WAF1 after ACNU treatment in the p53-null human osteosarcoma cell line Saos-2. These findings suggest that there are two possible pathways for WAF1 induction: the p53-dependent pathway through the p53-responsive element and the p53-independent pathway through other elements.
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PMID:p53-independent WAF1 induction by ACNU in human glioblastoma cells. 953 48

A human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53 gene, and clones of Saos-2 cells, which were transfected with wild type p53 or mutant p53 genes (123A, 143A, 175H and 273H), were observed for their surviving fraction after treatment with the commonly used anticancer drugs, cisplatin (CDDP), nimustine (ACNU), adriamicin (ADR) and bleomicin (BLM). The transfectants of the mutant 143A, 175H and 273H were significantly more resistant to CDDP than the transfectant of pOPI3 (expression plasmid only). The transfectants of the wild type p53 and mutant 123A were significantly more sensitive to ACNU than the transfectant of pOPI3. The transfectant of mutant 123A was more sensitive to ADR than the transfectant of pOPI3. There was no significant difference in sensitivity to BLM between Saos-2 and all kinds of transfectants. Thus the sensitivity of the cells to anticancer drugs varied with the mutation point of the p53 gene.
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PMID:Sensitivity of anticancer drugs in Saos-2 cells transfected with mutant p53 varied with mutation point. 956 97

We have constructed an in vitro system to examine how p53 mutants affect radiosensitivity. Mutations of p53 were made using in vitro mutagenesis, and mutant cDNAs were introduced into the human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53. For wild type p53, both the expression plasmid and a regulation plasmid (LacSwitch system) were transfected into the cells. The radiosensitivities of clones of mutant p53 and wild type p53 were examined. Transformants of wild type p53 had increased radiosensitivity. The induction of wild type p53 protein by addition of IPTG did not significantly increased radiosensitivity. A mutation at codon 123 also increased radiosensitivity. Mutations at codons 143, 175, and 273 did not alter radiosensitivity.
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PMID:Sensitivity to ionizing radiation in Saos-2 cells transfected with mutant p53 genes depends on the mutation position. 973 99


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