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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain insight into the cellular regulation of bovine leukemia virus (BLV) trans activation, a lambda-gt11 cDNA library was constructed with mRNA isolated from a BLV-induced tumor and the recombinant proteins were screened with an oligonucleotide corresponding to the tax activation-responsive element (TAR). Two clones (called TAR-binding protein) were isolated from 750,000 lambda-gt11 plaques. The binding specificity was confirmed by Southwestern (DNA-protein) and gel retardation assays. Nucleotide sequence analysis revealed that TAR-binding protein is very similar to the CREB2 protein. It contains a leucine zipper structure required for dimerization, a basic amino acid domain, and multiple potential phosphorylation sites. A vector expressing CREB2 was transfected into D17 osteosarcoma cells. In the absence of the tax transactivator, the CREB2 protein and the cyclic AMP-dependent protein kinase A activate the BLV long terminal repeat at a basal expression level: trans activation reached 10% of the values obtained in the presence of tax alone. These data demonstrate that CREB2 is a cellular factor able to induce BLV long terminal repeat expression in the absence of tax protein and could thus be involved in the early stages of viral infection. In addition, we observed that in vitro tax-induced trans activation can be activated or inhibited by CREB2 depending on the presence or absence of protein kinase A. These data suggest that the cyclic AMP pathway plays a role in the regulation of viral expression in BLV-infected animals.
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PMID:A cyclic AMP-responsive DNA-binding protein (CREB2) is a cellular transactivator of the bovine leukemia virus long terminal repeat. 130 10

Biological interactions between human cytomegalovirus (HCMV) and the human immunodeficiency virus type 1 (HIV-1) were analysed in transfection and infection experiments, carried out in a human osteogenic sarcoma cell line (HOS) and in the same cell line chronically infected with HCMV (E155). When HOS and E155 cells were transfected with recombinant plasmids containing the HIV long terminal repeat (LTR) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, LTR-directed CAT expression was 20 times higher in E155 cells than in HOS cells. HOS cells co-infected with HCMV and HIV-1 showed enhanced production of the HIV-1 p24 antigen. In reciprocal experiments, an increase in HCMV immediate early gene expression was observed when HCMV-infected HOS cells and E155 cells were either transfected with a recombinant plasmid containing the HIV transactivator gene (pTAT), or when infected with HIV-1. DNA hybridization analysis of E155 and HCMV-infected HOS cells revealed higher levels of HCMV DNA in cells transfected with pTAT than in cells transfected with other non-specific recombinant plasmids. E155 cells transfected with pTAT also produced higher titres of infectious HCMV than control cultures of E155 cells transfected with other recombinant plasmids, including pMTAT carrying a mutant tat gene. The functional reciprocity in vitro between HCMV and HIV is discussed with respect to its possible implications for the clinical development of AIDS.
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PMID:Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. 215 40

Transgenic mice overexpressing the c-fos proto-oncogene in bone develop osteosarcomas, whereas mice overexpressing c-Jun are normal. In this study, we investigated whether Fos and Jun would cooperate in vivo and whether the threshold levels of Fos are important in osteosarcoma formation. Fos-Jun double-transgenic mice develop osteosarcomas at a higher frequency than single-Fos transgenic mice with no differences in the time of onset of tumor formation. Histological and histochemical analyses indicated that Fos-Jun tumors contained greater quantities of neoplastic bone, were more remodeled, and contained a greater number of multinucleated osteoclast-like cells than tumors isolated from age-matched, single transgenic littermates. In contrast, overexpression of Fos in knockout mice that lack endogenous Fos resulted in a decrease in the number of tumor-bearing mice; osteosarcomas were almost absent in c-fos -/- mice, whereas tumor incidence was reduced to approximately 50% in c-fos +/- mice. Cell lines isolated from Fos-Jun transgenic tumors expressed high levels of both transgenes but significantly lower levels of the jun-related gene junB compared with cells expressing only a c-fos transgene. Osteoblastic marker genes were expressed at varying levels in different cell lines, but expression of interstitial collagenase (matrix metalloproteinase-1) was enhanced in cells derived from Fos-Jun tumors. These studies demonstrate that coexpression of a c-jun transgene can enhance Fos-induced oncogenesis in vivo and suggest that a critical level of Fos is necessary for osteosarcoma development.
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PMID:c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun and the role of endogenous c-fos. 852 21

Induction of immediate-early genes c-jun, junB, and c-fos was demonstrated during echovirus 1 infection in a human osteogenic sarcoma (HOS) cell line. Tenfold induction was seen at 10 h postinfection, corresponding approximately to the end of the first replication cycle of the virus. Echovirus 1 uses VLA-2 integrin as its cellular receptor, and ligand binding by integrin is known to trigger signal transduction pathways ultimately activating immediate-early genes. In the present study, however, VLA-2 binding alone was not sufficient to induce their expression; viral replication was needed. This conclusion was based on the observations that no stimulation of the immediate-early genes occurred in the MG-63 cell line where the virus attached only to VLA-2 but was not able to replicate and that induction of these genes was observed when the HOS cells were infected with echovirus type 7, known to use a different cellular receptor. Induction was not seen in the presence of the antiviral compound WIN 54954, which evidently inhibits the uncoating but not receptor binding of echovirus 1, suggesting that viral replication triggers the activation of the immediate-early genes. The induction of these genes may have a role in viral replication and in the pathogenesis of infection.
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PMID:Echovirus 1 replication, not only virus binding to its receptor, VLA-2, is required for the induction of cellular immediate-early genes. 909 4

We studied the expression of estrogen-related receptor ERR-1 during mouse embryonic development. ERR-1 mRNA is present in bones formed by both the endochondral and intramembranous routes, and the onset of its expression coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone. By gel shift analysis we found that ERR-1 binds as a monomer specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are required for efficient ERR-1 binding. In transient transfection assays, ERR-1 acts as a potent transactivator through the SFRE sequence. This effect is cell-specific since ERR-1 activates transcription in the rat osteosarcoma cell line ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2 cells. Notably, the osteopontin (a protein expressed by osteoblasts and released in the bone matrix) gene promoter is a target for ERR-1 transcriptional regulation. Our findings suggest a role for ERR-1 in bone development and metabolism.
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PMID:The ERR-1 orphan receptor is a transcriptional activator expressed during bone development. 917 50

We examined the phenotype of a herpes simplex virus (HSV) type 1 mutant (V422) in which the C-terminal acidic activation domain of the virion transactivator VP16 is truncated at residue 422. The efficiency of plaque formation by V422 on Vero cells was boosted by approximately 100-fold by including hexamethylene bis-acetimide (HMBA) in the growth medium, as previously observed with the in1814 VP16 linker insertion mutant isolated by Preston and colleagues. V422 displayed severely reduced levels of the immediate-early transcripts encoding ICP0 and ICP4 during infection in the presence of cycloheximide, and this defect was partially overcome by the addition of HMBA. The defect in plaque formation exhibited by V422 and in 1814 was efficiently complemented in U2OS osteosarcoma cells, which had previously been shown to complement ICP0 null mutations. Taken in combination, these data confirm the key role of VP16 in triggering the onset of the HSV lytic cycle.
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PMID:Truncation of the C-terminal acidic transcriptional activation domain of herpes simplex virus VP16 produces a phenotype similar to that of the in1814 linker insertion mutation. 922 15

Protein kinase CK2 (formerly casein kinase II) exhibits elevated expression in a variety of cancers, induces lymphocyte transformation in transgenic mice, and collaborates with Ha-Ras in fibroblast transformation. To systematically examine the cellular functions of CK2, human osteosarcoma U2-OS cells constitutively expressing a tetracycline-regulated transactivator were stably transfected with a bidirectional plasmid encoding either catalytic isoform of CK2 (i.e. CK2alpha or CK2alpha') together with the regulatory CK2beta subunit in order to increase the cellular levels of either CK2 isoform. To interfere with either CK2 isoform, cells were also transfected with kinase-inactive CK2alpha or CK2alpha' (i. e. GK2alpha (K68M) or CK2alpha'(K69M)) together with CK2beta. In these cells, removal of tetracycline from the growth medium stimulated coordinate expression of catalytic and regulatory CK2 subunits. Increased expression of active forms of CK2alpha or CK2alpha' resulted in modest decreases in cell proliferation, suggesting that optimal levels of CK2 are required for optimal proliferation. By comparison, the effects of induced expression of kinase-inactive CK2alpha differed significantly from the effects of induced expression of kinase-inactive CK2alpha'. Of particular interest is the dramatic attenuation of proliferation that is observed following induction of CK2alpha'(K69M), but not following induction of CK2alpha(K68M). These results provide evidence for functional specialization of CK2 isoforms in mammalian cells. Moreover, cell lines exhibiting regulatable expression of CK2 will facilitate efforts to systematically elucidate its cellular functions.
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PMID:Inducible expression of protein kinase CK2 in mammalian cells. Evidence for functional specialization of CK2 isoforms. 1031 65

Interferon (IFN) is an important immune system molecule capable of inducing an antiviral state within cells. Herpes simplex virus type 1 (HSV-1) replication is somewhat reduced in tissue culture in the presence of IFN, presumably due to decreased viral transcription. Here, we show mutations that inactivate immediate-early (IE) gene product ICP0 render HSV-1 exquisitely sensitive to IFN inhibition, resulting in greatly decreased levels of viral mRNA transcripts and the resulting polypeptides and a severe reduction in plaque formation ability. Mutations in other HSV-1 genes, including the genes coding for virion transactivator VP16 and the virion host shutoff protein vhs, IE gene ICP22, and the protein kinase UL13 gene, do not increase the IFN sensitivity of HSV-1. Interestingly, ICP0 mutants demonstrate the same level of sensitivity to IFN as wild-type virus on U2OS cells, an osteosarcoma cell line that is known to complement mutations in ICP0 and VP16. Thus, in some cell types, functional ICP0 is required for HSV-1 to efficiently bypass the inhibitory effects of IFN in order to ensure its replication. The significance of this link between ICP0 and IFN resistance is discussed.
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PMID:Herpes simplex virus ICP0 mutants are hypersensitive to interferon. 1064 80

Human T cell leukemia virus type I (HTLV-I) or its transcriptional transactivator, Tax1, was introduced into a human osteosarcoma cell line, HOS, and a Moloney murine sarcoma virus-positive HOS cell line, S+L-HOS. These HTLV-I- or Tax1-expressing cells were injected subcutaneously into nude mice to investigate the effects of HTLV-I on their tumorigenicities. HOS cells did not form any tumors even in the presence of HTLV-I or Tax1. S+L-HOS cells did form small tumors in two-thirds of nude mice. Infection of S+L-HOS cells with HTLV-I, or transduction of Tax1 into S+L-HOS cells markedly facilitated the tumor formation, and the tumor-bearing mice showed marked splenomegaly and neutrophilia. Elevated levels of granulocyte colony-stimulating factor (G-CSF) were detected in sera of these mice and also in the culture supernatants of Tax1-expressing human cells, suggesting that G-CSF in the mouse sera was produced by the human cells. In sera of some mice with splenomegaly and neutrophilia, high levels of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) were observed, suggesting that Tax1 produced by human cells induced mouse cells to produce mGM-CSF. Only S+L-HOS cell lines expressing Tax1 showed high tumorigenicity in nude mice. Thus, this system will be a useful model of tumor formation, splenomegaly and neutrophilia dependent on Tax1.
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PMID:Rapid tumor formation and development of neutrophilia and splenomegaly in nude mice transplanted with human cells expressing human T cell leukemia virus type I or Tax1. 1094 44

The BRCT (BRCA1 C-terminus) superfamily includes a large number of nuclear proteins closely involved in DNA repair, recombination, and cell-cycle control. The human cDNA clone NFBD1 (previously designated KIAA0170) encodes a novel protein (2089 amino acids in length; calculated molecular mass 226,440 D) with possible BRCT domains at its carboxy terminus (amino acid residues 1894-2089). This gene product has been described as one of the BRCT superfamily proteins. However, its biological significance has been unclarified. Expression of green fluorescent protein (GFP)-tagged full-length NFBD1 or a series of deletion mutants indicated that NFBD1 was localized to the nucleus in various mammalian cells, and a 197-amino acid segment near the amino terminus (amino acid residues 142-338) contained a nuclear targeting signal. In vitro DNA-binding experiments showed that the highly basic region of NFBD1 (amino acid residues 1841-1893) possessed DNA-binding activity. The region encoding amino acids 508-995 of NFBD1 fused inframe with GAL4 DNA-binding domain activated transcription in both yeast and mammalian cells, while the possible BRCT domains of NFBD1 failed to induce transcription in mammalian cells. Overexpression of antisense NFBD1 RNA in a p53-deficient human osteogenic sarcoma cell line (SAOS-2) resulted in remarkable suppression of SAOS-2 colony formation. These results suggest that NFBD1 is a nuclear transcriptional transactivator with possible BRCT domains and may contribute to cell growth control.
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PMID:NFBD1/KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain. 1097 65


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