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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transforming gene of simian sarcoma virus (SSV), an acute transforming retrovirus, and human platelet-derived growth factor (PDGF), a potent mitogen for connective tissue cells, appear to have arisen from the same or very closely related cellular genes. In an effort to obtain sufficient quantities of the SSV transforming gene product for the detailed analysis of its structural and biologic properties, we placed the v-sis gene under the control of strong phage transcriptional and translational signals that provide for regulated expression of cloned genes in E. coli. When induced, the bacterial cells synthesized levels of the SSV transforming gene product that constituted at least 10% of their total protein. Differences in the structure and processing of the v-sis gene product in procaryotic and eucaryotic cells provided important insights concerning posttranslational modifications of this PDGF-related transforming protein in eucaryotic cells.
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PMID:Expression of the PDGF-related transforming protein of simian sarcoma virus in E. coli. 631 11

A human clonal glioma cell line, U-343 MGa Cl 2, cultured under serum-free conditions, was found to release a factor that competed with 125I-labeled platelet-derived growth factor (125I-PDGF) for binding to human foreskin fibroblasts. The concentration of competing activity in conditioned medium was equal to 20-30 ng of PDGF per ml. The PDGF receptor competing activity had an elution position on Sephadex G-200 close to that of tracer PDGF. The same fractions in the chromatogram also contained growth-promoting activity and material active in a PDGF radioimmunoassay. Incubation of partially purified, 125I-labeled glioma factor with fibroblasts, or rabbit anti-PDGF serum, led to the selective binding of a component with an estimated Mr of 31,000, as shown by NaDodSO4/gel electrophoresis under nonreducing conditions. After reduction this component migrated as a Mr 18,000 protein. Thus, the behavior in NaDodSO4/gel electrophoresis was similar to that of PDGF. Furthermore, incubation of partially purified glioma factor with immobilized PDGF antibodies markedly decreased the amount of PDGF receptor competing activity remaining in the supernatant. These results suggest that the factor produced by glioma cells has structural, immunological, and functional resemblance to PDGF. We previously reported that a human osteosarcoma cell line produces a PDGF-like molecule with growth-promoting activity. Taken together with the recent finding that PDGF is homologous to the transforming gene product of simian sarcoma virus, our present data give additional support for the idea that an autocrine activation of the PDGF receptor may be operational in the growth of human tumors of mesenchymal or glial origin.
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PMID:A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity. 632 78

The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. It is unusual among haemopoietic cell lines in that one of these is c-sis, the gene from which the oncogene v-sis of the simian sarcoma virus was derived, and perhaps the gene for platelet-derived growth factor (PDGF). To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. This is the first example of transformation of NIH-3T3 cells by a human onc gene other than c-ras or Blym, as well as the first demonstration of transformation by a human cDNA clone.
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PMID:Transformation of NIH 3T3 cells by a human c-sis cDNA clone. 632 94

A series of nontransformed human and murine cells and derivative cell lines transformed by methylcholanthrene; by simian virus 40, Kirsten and Moloney murine sarcoma viruses, simian sarcoma virus, and adenovirus; and by a "spontaneous" event in culture were examined for the expression of receptors for the platelet-derived growth factor (PDGF) and for production of substances able to compete with 125I-labeled PDGF for binding to the cell-surface PDGF receptor. In each case, transformation resulted in a 50-100% decrease in available PDGF receptors. All transformed cells except the methylcholanthrene-transformed mouse cells produce a PDGF competitor into the conditioned medium. Levels of PDGF competitor in conditioned medium at the end of a 48-hr collection were as high as 2 ng/ml--high enough to be measured by radioreceptor assay diluted 1:30 and to maximally stimulate [3H]thymidine incorporation by human fibroblasts. The PDGF competitor activity detected in a radioreceptor assay does not reflect irreversible (e.g., proteolytic) damage to the receptor of test cells since its effects are reversed by acetic acid dissociation. Antiserum against human PDGF neutralizes 20-80% of the PDGF competitor found in conditioned medium from different transformed human cells and 100% of the activity from normal human endothelial cells. The possibility that induction of expression of the cellular PDGF gene may be involved in the mechanism of transformation of PDGF-responsive mesenchymal cells is discussed.
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PMID:Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. 632 25

The simian sarcoma virus transforming gene, v-sis, encodes a protein, p28sis , that is closely related to human platelet-derived growth factor (PDGF). The human locus related to v-sis was cloned and shown to contain at least five exons corresponding to the v-sis coding region. Nucleotide sequence analysis of these exons revealed that the predicted amino acid sequence of human c-sis differed by 6% from that of the woolly monkey-derived v-sis. These findings imply that the sis proto-oncogene has been well conserved during primate evolution. By comparison of the known amino acid sequences of PDGF peptides with the predicted human c-sis protein, it was possible to demonstrate that this human proto-oncogene is the structural gene encoding one of the two major polypeptides of this potent mitogen for connective tissue cells.
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PMID:Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor. 632 48

Normal rat kidney (NRK) cells transformed by simian sarcoma virus (SSV) release into the culture medium a biologically active mitogen with properties identical to those of human platelet-derived growth factor (PDGF). Like PDGF, the growth factor derived from SSV-NRK cells was shown to be stable to heat and sensitive to reducing agents. It was capable of inhibiting binding of labeled PDGF to the receptor on human fibroblasts. It also stimulated the phosphorylation of the same membrane protein (185 kilodaltons) in isolated plasma membranes from human fibroblasts. Immunoprecipitation of metabolically labeled proteins released by SSV-NRK cells showed that a 34-kilodalton protein was specifically precipitated by antiserum to PDGF. Upon reduction, this protein had a molecular size of 17 kilodaltons. PDGF has been shown to consist of two 14- to 18-kilodalton proteins linked by disulfide bonds.
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PMID:Simian sarcoma virus--transformed cells secrete a mitogen identical to platelet-derived growth factor. 632 59

The relationship between platelet-derived growth factor (PDGF) and the proto-oncogene c-sis has been determined by amino acid sequence analysis of PDGF and nucleotide sequence analysis of c-sis genomic clones. The nucleotide sequences of five regions of the human c-sis gene which are homologous to sequences of the transforming region (v-sis) of simian sarcoma virus (SSV) were determined. By alignment of the c-sis and v-sis nucleotide sequences the predicted amino acid sequence of a polypeptide homologous to the putative transforming protein p28sis of SSV was deduced. Both predicted sequences use the same termination codon and additional coding sequences may lie 5' to the homologous regions. Amino acid sequence analysis of the PDGF B chain shows identity to the amino acid sequence predicted from the c-sis sequences over 109 amino acid residues. Polymorphism may exist at two amino acid residues. These results suggest that c-sis encodes a polypeptide precursor of the B chain. A partial amino acid sequence of the PDGF A chain is also described. This chain is 60% homologous to the B chain and cannot be encoded by that part of c-sis which has been sequenced but could be encoded by sequences which lie 5' to the five regions of v-sis homology in c-sis, or at a separate locus.
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PMID:The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. 632 45

Antisera to synthetic peptides representing sequences of both chains of platelet-derived growth factor (PDGF) were used to structurally analyze PDGF isolated from outdated human platelets and PDGF-like proteins in normal and transformed cells. Most PDGF isolated from platelets did not contain the carboxyl portion of PDGF-2 in contrast to p20sis, the major form of p28sis detected in simian sarcoma virus-transformed cells. In addition, higher molecular weight forms of molecules containing PDGF-1 and PDGF-2 sequences were detected in all cell lines tested. These lines were heterogeneous with respect to species, cell type, and transforming agent.
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PMID:Detection of high molecular weight forms of platelet-derived growth factor by sequence-specific antisera. 649 5

Serum obtained by clotting whole blood contains a potent mitogen with apparent specificity for mesenchymal cells. This peptide wound-healing hormone, derived from platelets, is known as platelet-derived growth factor (PDGF). Serum obtained by clotting plasma contains no detectable growth-promoting activity for fibroblasts, and is therefore a valuable additive to culture medium for an examination of the autonomy of cells from exogenous PDGF. Fibroblasts from man, mouse and hamster remain mitotically quiescent in plasma-derived serum and proliferate only when a source of PDGF is added. Normal human kidney epithelial cells and human T-cells proliferate normally in plasma-derived serum, and are unaffected by the addition of PDGF. A range of virally transformed cells and malignant cells from chemically induced rodent sarcomas was tested for their proliferative capacity in plasma-derived serum and their response to exogenous PDGF. A complete spectrum of PDGF-dependence was revealed. Polyoma-transformed BHK21 cells and SV40-transformed 3T3 cells showed complete PDGF independence. Cells from 7 chemically induced rat or mouse sarcomas provided results which ranged from the FS6 (a C57BL Cbi mouse sarcoma which was completely PDGF dependent) to MC28 (a hooded rat sarcoma) which was completely PDGF independent. The dependence of proliferation of these cells on PDGF showed a close correlation with several features of their in vivo behaviour. Tumours which were non-immunogenic in syngeneic hosts, contained few host macrophages and produced a high incidence of spontaneous distant metastases provided PDGF-independent cells. Cells from highly immunogenic, macrophage-rich "non-metastasizing" tumours were on the other hand PDGF dependent and tumours of intermediate "malignancy" provided cells with partial autonomy from PDGF. An assay for anchorage-independent growth provided data which also correlated with autonomy from PDGF. However, daily addition of large amounts of PDGF to BHK21 C13 cells induced reversible anchorage independent growth. The value of plasma-derived serum for the investigation of the proliferative autonomy of malignant cells is emphasized.
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PMID:Platelet-derived growth-factor requirements for in vitro proliferation of normal and malignant mesenchymal cells. 722 84

Cells from a C57BL/cbi chemically induced fibrosarcoma (FS6) require exogenous platelet-derived growth factor (PDGF) for in vitro proliferation (as do normal "untransformed" fibroblasts) whereas cells obtained from the FS6M1 tumour, a spontaneous metastasizing subline, show autonomy from PDGF in vitro. Furthermore, the FS6 cells exhibit very low colony formation in an anchorage-independent growth assay. In vivo, this tumour is immunogenic, rarely metastasizes and is heavily infiltrated by host macrophages. Studies of in vitro cell proliferation and anchorage-independent growth show that syngeneic host macrophages from the peritoneal cavity or from the growing tumour release a diffusible factor(s) which has (1) growth-stimulating activity on FS6 cells in monolayer cultures in PDGF-poor medium and (2) potent colony-stimulating activity on FS6 cell cultured in methyl-cellulose-containing medium. These macrophage supernatants stimulate proliferation of quiescent normal fibroblasts in monolayer culture as well as FS6 sarcoma cells, but do not stimulate anchorage-independent growth of normal cells. Supernatants from BCG-elicited macrophages were shown to contain abundant arginase, and were cytolytic to FS6 cells but not to normal cells. Heat inactivation abrogated the arginase and cytotoxicity, revealing heat-stable mitogenicity for FS6 cells and normal fibroblasts. The stimulatory effect of macrophages on FS6 sarcoma cells can be mimicked by the addition of the tumour promoter 12-tetradecanoyl-phorbol-13-acetate (TPA) and supports the hypothesis that macrophages could play a significant role in multistage carcinogenesis by providing a source of endogenous promoter.
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PMID:Promotion of fibrosarcoma cell growth by products of syngeneic host macrophages. 729 7


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