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

The proto-oncogene c-fos is the cellular homologue of v-fos originally isolated from murine osteosarcoma. Fos protein is a major component of the AP-1 transcription factor complex, which includes members of the jun family. Stable expression of c-fos in mice has been demonstrated in developing bones and teeth, haematopoietic cells, germ cells and in the central nervous system. It has been proposed that c-fos has an important role in signal transduction, cell proliferation and differentiation. We have previously demonstrated that overexpression of c-fos in transgenic and chimaeric mice specifically affects bone, cartilage and haematopoietic cell development. To understand better the function of c-fos in vivo, we used gene targeting in embryonic stem cells to generate cells and mice lacking c-fos. Here we report that heterozygous fos +/- mice appear normal, although females exhibit a distorted transmission frequency. All homozygous fos -/- mice are growth-retarded, develop osteopetrosis with deficiencies in bone remodelling and tooth eruption, and have altered haematopoiesis. These data define the c-Fos protein as an essential molecule for the development of specific cellular compartments.
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PMID:Bone and haematopoietic defects in mice lacking c-fos. 146 44

The c-fos proto-oncogene, which is the normal homolog of the transforming gene carried by murine osteogenic sarcoma viruses, interacts with the protein product of another proto-oncogene, c-jun, to form a heterodimer that can recognize and bind to a specific sequence of nucleotides in the DNA. The expression of c-fos and c-jun is linked to the proliferation of certain cells and the differentiation of others, including those of monomyelocyte lineage. The authors used two cultured Hodgkin's Reed-Sternberg (H-RS) cell lines, KM-H2 and HDLM-1, and their single-cell clones to study the correlation of c-fos/c-jun expression with cell differentiation in H-RS cells. Within 48 hours after induction with phorbol ester (TPA), both parent lines exhibited markedly increased expression of c-fos/c-jun. The expression returned to the preinduction level after 96 hours, however, and the cells retained their differentiated status. The transitory increase in c-fos/c-jun expression suggests that binding of these proteins to a specific promoter in the nucleus triggers a cascade of events that result in cell differentiation. Expression of these proteins may not be required for the cells to maintain their differentiation. The authors selected three groups of sublines of HDLM-1 cells based on their degree of spontaneous cytologic differentiation. The first group, without obvious differentiation, showed a c-fos/c-jun expression pattern similar to that of the parent line. The second group, with moderate differentiation, had a high degree of expression, which decreased on treatment with TPA. The third group, which had morphologic features resembling those of histiocytes, expressed minimal amounts of c-fos/c-jun, irrespective of TPA treatment. These findings provide further evidence that c-fos/c-jun expression is related to differentiation of H-RS cells, and that these proteins are not byproducts of TPA induction. Expression of c-fos/c-jun also was noted in a subpopulation of H-RS cells in tissues; and this expression also was enhanced when these cells were treated with TPA in culture. These findings indicate that H-RS cells can differentiate to become mature-appearing cells in tissues.
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PMID:Correlation of c-fos/c-jun expression with histiocytic differentiation in Hodgkin's Reed-Sternberg cells. Examination in HDLM-1 subclones with spontaneous differentiation. 173 22

Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.
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PMID:Cyclic AMP blocks expression of the c-sis gene in tumor cells. 254 92

The proto-oncogene c-fos has been isolated as the cellular homolog of the v-fos gene found in the osteosarcoma inducing FBR- and FBJ-murine sarcoma viruses (MSV). Expression of the c-fos gene in transgenic mice leads to the development of bone lesions of which about half progress to bone tumors mainly chondrosarcomas. The tumors display a strong preference for males and have a latency with a mean of 9.5 months. However, also mice without visible lesions develop bone tumors with the same sex preference and latency. These consequences of c-fos expression are independent of the chosen promoter but dependent on a replacement of 3' noncoding sequences of c-fos by a long terminal repeat (LTR) of the FBJ-MSV virus.
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PMID:c-fos expression induces bone tumors in transgenic mice. 254 84

Expression of proto-oncogene fos is induced in response to a variety of growth factors and differentiation-specific agents. However, the induction of fos gene expression is not influenced by inhibition of protein synthesis. We, therefore, entertained the notion that expression of the fos gene may be governed by posttranslational modification of cellular transcriptional factors. We report here that transcription of the human c-fos gene is modulated by negatively and positively acting cellular factors. The nuclear protein products of the resident oncogene of the FBJ-murine osteosarcoma virus (v-fos) and its corresponding cellular proto-oncogene (c-fos) are stoichiometrically phosphorylated on serine and threonine residues. The c-fos protein is more highly phosphorylated than the v-fos protein due to the phosphorylation of unique sites tentatively localized to the c-terminal 20 amino acid residues. The protein kinase C agonist, TPA, stimulates phosphorylation of the c-fos, but not the v-fos protein.
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PMID:Proto-oncogene fos: factors affecting expression and covalent modification of the gene product. 283 Aug 21

We have investigated the covalent modification of the proteins encoded by the murine fos proto-oncogene (c-fos) and that of the corresponding gene product of FBJ murine osteosarcoma virus (v-fos). Both proteins are posttranslationally processed in the cell, resulting in forms with lower electrophoretic mobilities than that of the initial translation product on sodium dodecyl sulfate-polyacrylamide gels. Treatment with alkaline phosphatase indicates that most, if not all, of this electrophoretic shift is due to phosphoesterification of both proteins. These phosphoryl groups stoichiometrically modify the v-fos and c-fos proteins on serine residues and turn over rapidly in vivo in the presence of protein kinase inhibitors (half-life, less than 15 min). Direct quantitative comparison of steady-state labeling studies with L-[35S]methionine and [32P]phosphate reveals that the c-fos protein is four- to fivefold more highly phosphorylated than the v-fos protein is. Comparison of tryptic fragments from [32P]phosphate-labeled proteins indicates that although the two proteins have several tryptic phosphopeptides in common, the c-fos protein contains unique major tryptic phosphopeptides that the v-fos protein lacks. These unique sites of c-fos phosphorylation have been tentatively localized to the carboxy-terminal 20 amino acid residues of the protein. Phosphorylation of the c-fos protein, but not the v-fos protein, can be stimulated at least fivefold in vivo by the addition of either 12-tetradecanoyl-phorbol-13-acetate or serum. This increase in the steady-state degree of phosphorylation of c-fos appears to be independent of protein kinase C since phosphorylation is Ca2+ and diacylglycerol independent. The possible role of phosphorylation of these proteins in cellular transformation is discussed.
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PMID:Modification of fos proteins: phosphorylation of c-fos, but not v-fos, is stimulated by 12-tetradecanoyl-phorbol-13-acetate and serum. 311 Jun 3

The c-fos proto-oncogene is the cellular homologue of v-fos identified as the bone transforming gene of the FBJ and the FBR murine osteosarcoma viruses. We show here, using a sensitive in situ hybridization method, that the c-fos proto-oncogene is expressed in the cartilage, bone and tooth forming tissues during mouse development. This result suggests that the tumors observed after infection by the FBJ viral complex and c-fos overexpression in transgenic mice occur in those tissues in which c-fos is expressed during development.
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PMID:Expression of the c-fos proto-oncogene in bone, cartilage and tooth forming tissues during mouse development. 314 15

Regulation of transcription in eukaryotes is mediated by the specific interaction between cellular factors and promoter sequences. Cis-acting DNA sequences, frequently located upstream of the TATA box, have been implicated in modulating the expression of many genes. We are interested in the transcriptional regulation of proto-oncogenes because they may have a pivotal function in cell growth and differentiation. Expression of the proto-oncogene c-fos is induced in response to a variety of growth factors and differentiation-specific agents. The viral cognate of the c-fos gene is the resident transforming gene of FBJ-murine osteosarcoma virus which causes bone tumours in vivo and cellular transformation in vitro. We report here that transcription of the human c-fos gene is modulated by negatively and positively acting cellular factors.
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PMID:Modulation of c-fos gene transcription by negative and positive cellular factors. 356 89

SEWA tumour cells are derived from an osteosarcoma induced in an A.SW mouse by infection with polyoma virus. Cytogenetic analyses have revealed three different characteristic chromosomal abnormalities diagnostic for the presence of amplified genes: 'double minutes' (DMs), homogeneously staining chromosomal regions (HSRs) and C-bandless chromosomes (CMs; for review see ref. 2). DMs may undergo fluctuation in number depending on the conditions in which the cells grow. Their number usually increases after injection of cells into a mouse and often is reduced to undetectable levels when the cells are explanted back into tissue culture; when the cells are re-introduced into the mouse, they again acquire multiple DMs. We show here that cells of SEWA lines carrying DMs, HSRs or CMs contain amplified copies of the proto-oncogene c-myc and enhanced levels of c-myc messenger RNA and c-myc protein. DMs or CMs are the sites of c-myc amplification in two different SEWA lines.
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PMID:Amplification and enhanced expression of the c-myc oncogene in mouse SEWA tumour cells. 388 56

The transforming gene of the osteosarcoma-producing FBJ murine sarcoma virus, v-fos, is homologous to a normal cellular gene, c-fos, in vertebrate species. Transcripts from the c-fos proto-oncogene accumulate to very high levels in late gestational mouse and human extra-embryonic tissues. We now report that these RNA transcripts are translated in these tissues. Rabbits were immunized with a synthetic peptide whose sequence is common to both c-fos and v-fos. After affinity purification on an immunosorbent containing the fos peptide (a nonapeptide), the antibody reacted with a component(s) in nuclei in sections of human and murine tissues and immunoprecipitated the v-fos gene product (p55) and a cellular protein of 39 kd (p39, complexed with fos) from lysates of metabolically-labelled virally transformed cells. Crude extracts of normal tissues contained major anti-fos-reactive proteins in the range of 55-60 kd as shown by protein blot analysis. Indirect immunofluorescence and immunoperoxidase staining showed that in addition to strong immunoreactive component(s) in the nuclei of extra-embryonic tissues of human and mouse, weaker reactions are detectable in all normal fetal and adult tissues tested. This demonstrates that fos-reactive protein is expressed in a wide variety of cells and tissues.
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PMID:Product of the cellular oncogene, c-fos, observed in mouse and human tissues using an antibody to a synthetic peptide. 389 12


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