Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunostaining methods were used to detect viral T-antigen and the cellular protein p53 in pathological tissues obtained from transgenic mice carrying JC-SV40 hybrid viral DNAs. A transgenic mouse carrying the SV40 regulatory region and JC virus (JCV) T-antigen-coding sequences exhibited an SV40-characteristic choroid plexus papilloma that expressed JCV T-antigen and p53. JCV-associated pathology was observed in two other mice in which the JCV regulatory signals directed SV40 T-antigen-induced adrenal neuroblastomas and brain neoplastic cells. However, these mice also exhibited an SV40-characteristic osteosarcoma and abdominal lymphoma that contained SV40 T-antigen and p53-positive cells. Contrasting thymic pathology was observed in the two types of mice where the SV40 regulatory region directed a JCV T-antigen-induced thymoma in one mouse, and the JCV regulatory region directed SV40 T-antigen-induced thymic hypoplasia in two other mice.
Mol Chem Neuropathol 1993 Sep
PMID:Expression of viral T-antigen in pathological tissues from transgenic mice carrying JC-SV40 chimeric DNAs. 825 Oct 33

Uncontrolled cell growth is at the basis of neoplastic proliferation and arteriosclerotic lesions. In vitro proliferation of vascular smooth muscle cells, Balb c/3T3 fibroblasts, retinal neuroepithelial cells and neuroblastoma cells is inhibited by d-alpha-tocopherol. On the contrary Chinese hamster ovary cells, osteosarcoma cells and macrophages are not sensitive. PDGF-BB activated proliferation is highly d-alpha-tocopherol sensitive while lysophosphatidic acid induced growth is poorly inhibited. d-beta-Tocopherol, an analogue of d-alpha-tocopherol, with similar antioxidant properties, does not inhibit proliferation. Protein kinase C activity is inhibited by d-alpha-tocopherol but not by d-beta-tocopherol, suggesting a central role of this enzyme in the control of cell proliferation by d-alpha-tocopherol. Activation of the transcription activation complex AP-1 (but not NFKB) is prevented by d-alpha-tocopherol and not by d-beta-tocopherol.
Mol Aspects Med 1993
PMID:d-alpha-tocopherol control of cell proliferation. 826 42

A regulatory mechanism for the vitamin D receptor (VDR) in rat osteosarcoma cells (ROS 17/2.8) is stabilization of the receptor through binding of its ligand, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Increased transcription of the gene encoding VDR does not occur upon treatment of these osteoblast-like cells with 1,25-(OH)2D3. When 10 nM 1,25-(OH)2D3 was administered to confluent cultures of ROS 17/2.8 cells, no change in receptor mRNA was detected, as measured by a ribonuclease protection assay. VDR abundance was measured using an immunoradiometric assay at varying time points within a 24-h period after 1,25-(OH)2D3 treatment. Receptor protein levels increased rapidly and continued to rise over 24 h. By 2 h, the level of receptor increased 2.5-fold, achieving a maximum level of 8-fold above the baseline at 18 h. The half-life of the receptor protein is 2 h in the absence of hormone, as determined by blockage of translation in cycloheximide-treated cells. In the presence of hormone, however, receptor levels were unchanged for at least 6 h. The administration of 1,25-(OH)2D3 stabilizes the receptor, thereby resulting in its accumulation in ROS 17/2.8 cells.
Mol Endocrinol 1993 Oct
PMID:Stabilization of the vitamin D receptor in rat osteosarcoma cells through the action of 1,25-dihydroxyvitamin D3. 826 62

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.
Mol Carcinog 1993
PMID:Dependence of induction of osteocalcin gene expression on the presence of wild-type p53 in a murine osteosarcoma cell line. 828 Mar 78

The MYC proto-oncogene has been shown to be overexpressed in several types of sarcomas, including some osteosarcomas. In most cases, the overexpression is due to gene amplification. The total number of osteosarcoma patients studied, however, remains too small to derive any conclusions regarding the true prevalence and the possible clinical significance of MYC gene amplification. To address the issue more thoroughly, we studied 27 specimens from 25 patients with high-grade osteosarcoma (16 primary, 11 metastatic; 11 adult, 14 pediatric) for MYC gene alterations by Southern blot analysis. Two of 27 specimens (7%) showed MYC gene amplification: a primary fibrohistiocytic osteosarcoma of the femur in a 37-year-old man showed threefold amplification, and a primary Paget's osteosarcoma of the tibia in a 60-year-old man showed fourfold amplification. None of the specimens tested showed MYC gene rearrangement (zero of 27) or activating point mutations at the PvuII site in MYC exon-1 (zero of 26). Hence, the MYC gene is amplified in a subset of osteosarcomas. The possible clinical or biological significance of MYC gene amplification in osteosarcoma may warrant further investigation.
Diagn Mol Pathol 1993 Sep
PMID:Sporadic amplification of the MYC gene in human osteosarcomas. 828 30

The oncogene mdm2 has been found to be amplified in human sarcomas, and the gene product binds to the tumor suppressor p53. In this report, we describe the dissection of the MDM2-binding domain on p53 as well as the p53-binding domain on MDM2. We also demonstrate that the oncoprotein simian virus 40 T antigen binds to the product of cellular oncogene mdm2. We have constructed several N- and C-terminal deletion mutants of p53 and MDM2, expressed them in vitro, and assayed their in vitro association capability. The N-terminal boundary of the p53-binding domain on MDM2 is between amino acids 1 and 58, while the C-terminal boundary is between amino acids 221 and 155. T antigen binds to an overlapping domain on the MDM2 protein. On the other hand, the MDM2-binding domain of p53 is defined by amino acids 1 and 159 at the N terminus. At the C terminus, binding is progressively reduced as amino acids 327 to 145 are deleted. We determined the effect of human MDM2 on the transactivation ability of wild-type human p53 in the Saos-2 osteosarcoma cell line, which does not have any endogenous p53. Human MDM2 inhibited the ability of human p53 to transactivate the promoter with p53-binding sites. Thus, human MDM2 protein, like the murine protein, can inactivate the transactivation ability of human p53. Interestingly, both the transactivation domain and the MDM2-binding domain of p53 are situated near the N terminus. We further show that deletion of the N-terminal 58 amino acids of MDM2, which eliminates p53 binding, also abolishes the capability of inactivating p53-mediated transactivation. This finding suggests a correlation of in vitro p53-MDM2 binding with MDM2's ability in vivo to interfere with p53-mediated transactivation.
Mol Cell Biol 1993 Nov
PMID:The tumor suppressor p53 and the oncoprotein simian virus 40 T antigen bind to overlapping domains on the MDM2 protein. 841 78

Alkaline phosphatase (AP) activity and expression of bone Gla protein (BGP), c-fos, and c-jun were compared in two transplantable osteosarcomas with high potentials for metastasis to the lung. The original spontaneous osteosarcoma (SOS) gradually became histologically undifferentiated, losing its osteogenic activity during serial transfer, whereas the chemical (4-hydroxyaminoquinoline 1-oxide)-induced osteosarcoma (COS) retained osteogenesis. The two osteosarcomas showed similar doubling times and levels of lung metastasis, and strong AP activity was detected on the cell membranes of both. Northern blot analysis revealed that lack of BGP mRNA expression was associated with expression of both c-fos and c-jun proto-oncogenes in SOS. In contrast, neither c-fos nor c-jun mRNAs were detected but BGP mRNA was expressed in the case of COS. These results suggest that the c-fos and c-jun genes may suppress the expression of BGP mRNA relevant to differentiation and osteoid formation in rat osteosarcomas. However, this does not appear to be directly related to proliferative or metastatic biological behavior.
Mol Carcinog 1993
PMID:Correlation between lack of bone Gla protein mRNA expression in rat transplantable osteosarcomas and expression of both c-fos and c-jun proto-oncogenes. 845 89

The present study was undertaken to examine oncogene abnormalities in human bone and soft tissue tumors. Twenty four tumor tissues and one human cell strain established from an osteosarcoma were examined by Southern blot analysis using a recessive oncogene (p0.9R and p3.8R derived from a cDNA of the Rb gene) and eight dominant oncogenes (c-myc, c-K-ras, c-fos, c-raf-1, c-fms, c-sis, N-myc, and c-erb B) as probes. Homozygous deletions or other alterations within the Rb locus were found in 3 of 6 osteosarcomas, 1 osteosarcoma cell line, 1 of 3 malignant fibrous histiocytomas and 1 of 2 Ewing's sarcomas. On the other hand, amplification of c-myc was found in 2 osteosarcomas and 1 osteosarcoma cell line. All cases with c-myc amplification had alterations in the structure of the Rb locus, and these patients showed rapid clinical malignancy progression and a probable tendency to bone metastases. Results of this study suggest that structural alterations of the Rb gene and amplification of c-myc might play an important role in the clinical course and pathogenesis of osteosarcoma.
Cell Mol Biol (Noisy-le-grand) 1993 Mar
PMID:Alterations of retinoblastoma susceptible gene accompanied by c-myc amplification in human bone and soft tissue tumors. 851 77

U2OS Dr1 cells, originating from a human osteosarcoma, are resistant to the intracellular action of diphtheria toxin but contain toxin receptors on their surfaces. These cells do not have detectable amounts of fibroblast growth factor receptors. When these cells were transfected with fibroblast growth factor receptor 4, the addition of acidic fibroblast growth factor to the medium induced tyrosine phosphorylation, DNA synthesis, and cell proliferation. A considerable fraction of the cell-associated growth factor was found in the nuclear fraction. When the growth factor was fused to the diphtheria toxin A fragment, it was still bound to the growth factor receptor and induced tyrosine phosphorylation but did not induce DNA synthesis or cell proliferation, nor was any fusion protein recovered in the nuclear fraction. On the other hand, when the fusion protein was associated with the diphtheria toxin B fragment to allow translocation to the cytosol by the toxin pathway, the fusion protein was targeted to the nucleus and stimulated both DNA synthesis and cell proliferation. In untransfected cells containing toxin receptors but not fibroblast growth factor receptors, the fusion protein was translocated to the cytosol and targeted to the nucleus, but in this case, it stimulated only DNA synthesis. These data indicate that the following two signals are required to stimulate cell proliferation in transfected U2OS Dr1 cells: the tyrosine kinase signal from the activated fibroblast growth factor receptor and translocation of the growth factor into the cell.
Mol Cell Biol 1996 Jan
PMID:Stimulation of proliferation of a human osteosarcoma cell line by exogenous acidic fibroblast growth factor requires both activation of receptor tyrosine kinase and growth factor internalization. 852 4

Although numerous studies have shown potent antiproliferative and differentiation-inducing effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and its analogs on cells not directly related to bone metabolism, only few reports focussed on the effects of these analogs on bone. We compared the action of several recently developed analogs with that of 1,25-(OH)2D3 on human (MG-63) and rat (ROS 17/2.8) osteoblast-like cells and on in vitro bone resorption. In MG-63 cells the analogs EB1089 and KH1060 were about 166,000 and 14,000 times more potent than 1,25-(OH)2D3 in stimulating type I procollagen and 100 and 6,000 times more potent in stimulating osteocalcin production, respectively. Also in ROS 17/2.8 cells EB1089 and KH1060 were most potent in inducing osteocalcin synthesis. In vitro bone resorption was 2.3 and 17.5 times more potently stimulated by EB1089 and KH1060, respectively. In MG-63 cells, 1,25-(OH)2D3 and the analogs inhibited cell proliferation, whereas both 1,25-(OH)2D3 and the analogs stimulated the growth of ROS 17/2.8 cells. Differences in potency could neither be explained by affinity for the vitamin D receptor nor by a differential involvement of protein kinase C in the action of the analogs. Together, these data show that also in bone the analogs EB1089 and KH1060 are more potent than 1,25-(OH)2D3 but that the potency of the analogs compared to 1,25-(OH)2D3 is dependent on the biological response. On the basis of these observations it can be concluded that the reported reduced calcemic effect in vivo is not the result of a decreased responsiveness of bone to these analogs. Lastly, in view of eventual clinical application of 1,25-(OH)2D3-analogs, the observed stimulation of in vitro bone resorption and growth of an osteosarcoma cell line warrant in vivo studies to further examine these effects.
J Steroid Biochem Mol Biol 1995 Dec
PMID:Differential effects of 1,25-dihydroxyvitamin D3-analogs on osteoblast-like cells and on in vitro bone resorption. 854 Dec 30


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