Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preparations of the mitogen platelet-derived growth factor (PDGF) from human platelets contain two related polypeptides termed A chain and B chain. PDGF-B is highly homologous to a portion of p28v-sis, the transforming protein of simian sarcoma virus. We have studied the mitogenic potential of a PDGF-BB-like homodimer by expressing the sequence coding for the mature part of PDGF-B in Escherichia coli. Expression was achieved as cro-beta-gal-PDGF-B fusion protein which was exclusively found in the "inclusion bodies". A monomeric PDGF-B fragment shortened by 12 amino acid residues from the NH2 terminus was excised from the fusion protein by CNBr cleavage. After protection of thiols by S-sulfonation, this fragment was purified by gel permeation chromatography and reversed-phase high-performance liquid chromatography. This monomeric protein was dimerized in the presence of a mixture of reduced and oxidized glutathione to yield biologically active rPDGF-BB with an overall yield of approximately 0.7 mg of rPDGF-BB/L of culture. Escherichia coli rPDGF-BB stimulated [3H]thymidine incorporation into AKR2B fibroblast at concentrations of about 1 ng/mL.
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PMID:Preparation of biologically active platelet-derived growth factor type BB from a fusion protein expressed in Escherichia coli. 266 65

Cell lines derived from human sarcomas have been previously shown to produce a protein growth factor which, similar to platelet-derived growth factor (PDGF), can induce competence for mitosis in fibroblasts. Whether this factor production is an important feature of sarcomas in vivo or simply an artefact caused by long-term culture conditions is unclear, however. We demonstrated growth factor activity in conditioned medium from six of 11 primary sarcoma cultures, utilizing flow cytometric analysis of DNA to monitor the presence of sarcoma cells in cultures. Cells isolated from control tissues failed to show a similar mitotic effect.
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PMID:Growth factor production by sarcoma cells in primary culture. 273 65

Six biopsies (4 of human fibrosarcomas, 1 of a B-cell lymphoma and 1 of a normal lymph node from a melanoma patient) and 6 cell lines (derived from 5 different human osteosarcomas and from 1 rhabdomyosarcoma), together with control cells, were examined for the expression of c-sis, c-fos and c-myc. The expression of c-sis/PDGF-B-related proteins was also examined in cultured cells (not in biopsies). In situ hybridization studies further showed that the occurrence and level of expression of c-sis mRNA and c-sis/PDGF-B-related proteins were significant in the tumor cells. Expression of c-fos and c-myc mRNA did not correlate with c-sis expression. Southern blot analysis of c-sis, c-fos and c-myc of 20 DNAs of cell lines derived from human sarcoma or biopsies showed an identical pattern for BamH1 and EcoR1 restriction fragments of c-sis (except for 1 fibrosarcoma biopsy), implicating no gene rearrangement as a cause of enhanced proto-oncogene expression. The nucleotide sequence of c-sis is highly homologous to that of the viral v-sis oncogene which is capable of transforming infected cells. We conclude that enhanced expression of c-sis in the sarcomas we have examined is involved in the initiation and/or maintenance of the cell transformed state.
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PMID:Expression of c-sis and other cellular proto-oncogenes in human sarcoma cell lines and biopsies. 279 39

SRI 62-834, an analog of the antitumor agent ET-18-OCH3 in which the oxygen atom at carbon atom 2 has been incorporated into a five-membered heterocycle, has been prepared and evaluated as an antitumor agent. The compound exhibited good cytotoxicity in vitro against a variety of tumor cell lines and was as effective as ET-18-OCH3 given orally in the mouse Meth A sarcoma model. SRI 62-834 was shown to be an inhibitor of platelet-derived growth factor (PDGF), possibly at the receptor level, and platelet-activating factor (PAF) at the receptor level.
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PMID:Antitumor activity of SRI 62-834, a cyclic ether analog of ET-18-OCH3. 283 80

The protein encoded by v-sis, the oncogene of simian sarcoma virus, is homologous to the B chain of platelet-derived growth factor (PDGF). There are eight conserved Cys residues between PDGF-B and the v-sis protein. Both native PDGF and the v-sis protein occur as disulfide-bonded dimers, probably containing both intramolecular and intermolecular disulfide bonds. Oligonucleotide-directed mutagenesis was used to change the Cys codons to Ser codons in the v-sis gene. Four single mutants lacked detectable biological activity, indicating that Cys-127, Cys-160, Cys-171, and Cys-208 are required for formation of a biologically active v-sis protein. The other four single mutants retained biological activity as determined in transformation assays, indicating that Cys-154, Cys-163, Cys-164, and Cys-210 are dispensable for biological activity. Double and triple mutants containing three of these altered sites were constructed, some of which were transforming as well. The v-sis proteins encoded by biologically active mutants displayed significantly reduced levels of dimeric protein compared with the wild-type v-sis protein, which dimerized very efficiently. Furthermore, a mutant with a termination codon at residue 209 exhibited partial transforming activity. This study thus suggests that the minimal region required for transformation consists of residues 127 to 208. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the v-sis proteins encoded by some of the biologically active mutants exhibited an altered conformation when compared with the wild-type v-sis protein, and suggested that Cys-154 and Cys-163 participate in a nonessential disulfide bond.
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PMID:Identification of nonessential disulfide bonds and altered conformations in the v-sis protein, a homolog of the B chain of platelet-derived growth factor. 283 54

The platelet-derived growth factor (PDGF) is a potent mitogen for cells derived from mesenchyme and is highly related to the transforming protein of the simian sarcoma virus (SSV), p28v-sis. Both PDGF and p28v-sis appear to initiate DNA synthesis and cell proliferation through an interaction with PDGF cell surface receptors but the identity of the PDGF induced signals which are recognized within the nucleus is unknown. It has been suggested that PDGF is directly transported to the nucleus although conflicting data have been obtained when nuclear fractions have been analysed for PDGF-like proteins. Specific antisera recognizing PDGF and p28v-sis were used to isolate and partially characterize proteins from nuclei of SSV-transformed NRK fibroblasts. Nuclear proteins of 66, 65, and 44 kD were identified in immunoprecipitates. These proteins were displaced competitively from binding to anti-PDGF antisera by either PDGF or by mitogenically active recombinant v-sis protein homodimers and the proteins were not recognized by non-immune sera. Proteins of 66, 65, and 44 kD also were partially purified from nuclear extracts with anti-PDGF immunoaffinity chromatography and were identified in silver stained PAGE gels. The data establish the presence of proteins antigenically related to PDGF within the nuclei of SSV-transformed cells and suggest possible roles of nuclear proteins related antigenically to PDGF and p28v-sis in cell growth and transformation.
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PMID:Identification and purification of PDGF/sis-like proteins from nuclei of simian sarcoma virus-transformed fibroblasts. 283 37

Antiserum to human platelet-derived growth factor (PDGF) recognized a simian sarcoma virus transformation-specific glycopeptide, now termed gp200sis, thereby establishing an immunological relationship between PDGF and this highly glycosylated molecule. The same antibodies as well as an antiserum against SSV-NP cells reacted with isolated gp200sis after immunoprecipitation, SDS-PAGE, and electroelution. In analogy to PDGF, the gp200sis protein backbone is shown here to consist of disulfide-linked polypeptide chains. On SDS-PAGE under nonreducing conditions, the deglycosylated molecule migrated as two dimers with molecular weights of 26 and 28 kDa, respectively. Preliminary functional studies indicate that SSV nonproducer cells secrete high-molecular-weight mitogens (greater than 150 kDa) that are specific for SSV-induced transformation. We suggest that gp200sis acts as a PDGF-like growth factor.
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PMID:Highly glycosylated PDGF-like molecule secreted by simian sarcoma virus-transformed cells. 283 58

Transformation by the v-sis containing simian sarcoma virus (SSV) is believed to be mediated by constitutive production of a platelet-derived growth factor (PDGF)-like molecule and its interaction with the PDGF receptor. SSV-transformed nonproducer NRK cells release into their tissue culture supernatant a high-molecular-weight factor (150-300 kDa) with biological activities closely resembling those of human PDGF. The partially purified high-molecular-weight factor competes with 125I-PDGF for receptor binding and leads to growth stimulation and anchorage-independent growth of normal cells. All these activities can be blocked by antibodies against PDGF and SSV-NP cells. The formerly described SSV transformation-specific glycopeptide (Thiel and Hafenrichter, 1984), now termed gp200sis, is recognized by the same specific antibodies and shows a striking resemblance in size. We conclude that gp200sis is responsible for the described PDGF-like activities.
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PMID:A high-molecular-weight PDGF-like factor secreted by v-sis transformed cells leads to growth stimulation and transformation. 284 Jun 22

The genes for platelet-derived growth factor (PDGF) A chain, B chain/c-sis, and the PDGF receptor are expressed in human malignant glioma cell lines. In the present investigation we have studied the expression of these genes in biopsy specimens from human glioblastomas. Hyperplasia of the vascular endothelium is a prominent characteristic of human glioblastoma multiforme and simian sarcoma virus-induced gliomas in primates. RNA transfer blot analysis of biopsies from glioblastoma multiforme showed transcripts for PDGF A and B chains and the PDGF receptor. Tissue sections from this tumor examined by in situ hybridization techniques revealed that the proliferating vascular endothelial cells contained large quantities of mRNA for PDGF B chain/c-sis and its receptor and, to a lesser extent, for PDGF A chain. In contrast, the tumor cells expressed more mRNA for PDGF A chain than for PDGF B chain and PDGF receptor. The latter two were also expressed at higher levels in glioma cells than in glial cells of nontumorous human brain tissue. Thus, an autocrine stimulation by the PDGF B chain/c-sis product via its receptor, evoked by interaction with surrounding glioma cells, could be the mechanism behind the pathological proliferation of endothelial cells characteristically found in this type of malignancy.
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PMID:Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation. 284 20

Calf serum induced the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney (NRK) cells transformed by a temperature-sensitive Kirsten murine sarcoma virus (tsK-NRK cells). Various growth factors known to induce the phospholipase C reactions in other cell types, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, thrombin, vasopressin, bombesin, cholecystokinin, and prostaglandin F2 alpha, did not induce phospholipase C reactions in the transformed NRK cells. Furthermore, noradrenaline, histamine, dopamine, angiotensin II, carbachol, and tumor growth factor-beta did not induce phospholipase C reactions. However, serotonin did induce phospholipase C reactions. The amount of serotonin contained in the calf serum was sufficient to support 50% of the activity promoted by the serum itself, and calf serum-induced phospholipase C reactions were inhibited to 10-20% of the original level by ketanserin and methysergide, known to be antagonists for the serotonin receptors. Dialysis almost completely removed serotonin from calf serum and reduced the serum-induced phospholipase C reactions. Moreover, the phospholipase C reactions induced by calf serum and serotonin were inhibited by pretreatment of the cells with pertussis toxin or 12-O-tetradecanoylphorbol-13-acetate. These results indicate that serotonin is one of the major serum factors inducing phospholipase C-mediated hydrolysis of phosphoinositides in transformed NRK cells. Serotonin induced phospholipase C reactions not only in tsK-NRK cells but also in nontransformed NRK cells. However, serotonin did not induce these reactions in Swiss 3T3 cells or NIH 3T3 cells.
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PMID:Serotonin as a major serum factor inducing the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney cells. 284 56


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