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

The aberrant expression of a protein that is involved in normal growth regulatory pathways can cause cell transformation. One of the best examples of this phenomenon is the transformation of fibroblasts by the simian sarcoma virus (SSV). An oncogene (v-sis) of this virus encodes a protein whose amino acid sequence is highly homologous to one of the subunits of a mesenchymal cell mitogen, platelet-derived growth factor (PDGF). How does expression of the v-sis or related genes transform cells? Clearly, this process uses biochemical pathways involved in the normal actions of growth factors. For example, the v-sis-encoded protein appears to act through cellular PDGF receptors. The biochemical consequences of PDGF receptor activation include increased tyrosine kinase activity, enhanced expression of a set of genes associated with cell proliferation, the dramatic alteration in cellular cytoskeleton, a rapid turnover of membrane phospholipids and the commitment of the cell to proceed through a series of responses culminating in the replication of DNA. An important issue is whether, in SSV transformed cells, these biochemical pathways are simply overstimulated by an abundance of self-made growth factor, or are there qualitative alterations in the pathways that are unique to these cells. Several specific related questions are addressed in this discussion: Is the protein encoded by the v-sis gene functionally identical to PDGF? Does the v-sis-encoded protein act at the cell surface or at intracellular sites? In the action of PDGF-like compounds, what are the biochemical steps distal to receptor stimulation?(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The sis gene and PDGF. 353 86

Human platelet-derived growth factor is the major mitogen in serum for connective-tissue-derived cells in culture. The factor is 30,000 mol. wt protein composed of two disulphide-linked polypeptide chains, named A and B. The B-chain is virtually identical to part of the transforming protein of simian sarcoma virus (SSV), implying that SSV-transformation is mediated by a PDGF-like growth factor. This notion is supported by the finding that specific as well as nonspecific inhibitors of PDGF-action (PDGF antibodies and suramin, respectively) are efficient inhibitors of SSV-transformation and revert the transformed phenotype of SSV-transformed cells. Expression of the genes encoding the PDGF subunits and production of PDGF-like growth factors is a common feature of human sarcoma cell lines, suggesting a role of PDGF in the pathogenesis of sarcomas, although direct support in favor of this notion is lacking. An involvement of PDGF in autocrine and paracrine stimulation of normal cell growth is suggested by the finding that responsive (arterial smooth muscle cells and placental cytotrophoblasts) as well as nonresponsive (endothelial cells and macrophages) cells produce PDGF-like growth factors. In conclusion, PDGF-like growth factors may be widely implicated in normal as well as neoplastic growth processes.
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PMID:Platelet-derived growth factor as a mediator of normal and neoplastic cell proliferation. 354 31

Human platelet-derived growth factor (PDGF) is a potent mitogenic polypeptide which is believed to be a heterodimer of A- and B-chains stabilized by interchain disulphide bonds. The B-chain of PDGF is encoded by the c-sis gene, the normal cellular homologue of the transforming gene of the simian sarcoma virus (SSV). cDNA clones of the B-chain from both normal and transformed cells have mutually consistent DNA sequences. Recently, an A-chain cDNA clone (D-1) was isolated from a transformed human glial cell cDNA library. We report the complete sequence of an A-chain cDNA clone (BT-1) isolated from a normal human umbilical vein endothelial (HUVE) cell cDNA library. BT-1 differs from the sequence of the D-1 clone by a 69 base pair deletion containing the predicted carboxy terminus of the protein. The mRNA levels of the A- and B-chains of PDGF in HUVE cells were analysed and shown to respond differently to the endothelial cell growth factor (ECGF).
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PMID:cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains. 361 63

The structure and genetic organization of the transcription unit of the c-sis proto-oncogene was determined. Comparative nucleotide sequence analysis of the exon sequences of feline and human c-sis revealed a very high degree of homology. The cap site as well as the poly(A)-addition site of the sis transcript of each species was identified and found in similar positions. An insert of 4 amino acids was found in the deduced translational product of feline c-sis and it was located at the amino-terminus of the region that constituted the platelet-derived growth factor domain. An insert of 149 bp present at the 5' end of exon 7 of human c-sis but absent in the simian sarcoma virus v-sis oncogene was also present in the feline c-sis proto-oncogene.
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PMID:Genetic organization of the c-sis transcription unit. 382 31

Several oncogenes are thought to cause transformation by affecting the signal transmission pathway of growth factors. One example is the induction of c-myc, the cellular homologue of the avian transforming oncogene v-myc, by platelet-derived growth factor (PDGF) among a set of genes associated with competence induction in fibroblasts. Another of the competence genes, r-fos, has been shown to be related to v-fos, the transforming gene of the FBJ sarcoma virus. In addition, PDGF induces c-fos, the cellular homologue of v-fos. The importance of c-myc induction is suggested by the observation that c-myc, under the control of a glucocorticoid regulator, can partially relieve the requirement of fibroblasts for PDGF. We have examined the effects of oncogenes on haematopoietic/lymphoid cell differentiation, immortalization and factor dependence for growth. Here we report the effects of recombinant murine retroviruses capable of expressing the avian v-myc. With interleukin-3 (IL-3)- or interleukin-2 (IL-2)-dependent cells, the viruses abrogated the requirement for growth factors and suppressed c-myc expression.
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PMID:Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes. 393 Sep 72

Vascular endothelial cells have a central role in various pathophysiological responses such as acute inflammation, wound healing and atherogenesis. The anatomical position of endothelial cells between blood leukocytes and the surrounding vascular smooth muscle cells or stromal fibroblasts may intensify and focus the effects of released endothelial cell products. Endothelial cells in culture produce a platelet-derived growth factor (PDGF)-like mitogen. PDGF purified from platelets is a basic protein with an apparent relative molecular mass (Mr) of approximately 30,000 (reviewed in refs 2, 3) and is believed to comprise two polypeptide chains, PDGF-A and PDGF-B (also referred to as PDGF-1 and PDGF-2; refs 5, 6). Sequence analysis of PDGF B chain has revealed a striking homology with the predicted sequence of p28sis, the transforming protein of simian sarcoma virus. sis-Homologous transcripts have been detected by Northern blot analysis of RNA from cultured endothelial cells. However, there are no structural data available on either the protein product or the messenger RNA to establish the identity of the endothelial-derived mitogen with either chain of PDGF. Here we report the isolation and complete sequence analysis of a sis-homologous complementary DNA clone from human endothelial cells, providing an opportunity to study the structure of sis as transcribed by a normal (untransformed) cell. Our results establish that normal human endothelial cells in culture express the B chain of PDGF, and that endothelial-derived PDGF B chain is synthesized as a predicted precursor polypeptide of Mr 27,281.
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PMID:Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. 403 72

Quiescent mouse BALB/c-3T3 cells were treated with beta-interferon to induce the secretion of proteins of 30 and 89 kDa and with a platelet-derived growth factor preparation to induce the secretion of a 63-kDa protein. To label the secreted proteins the cultures were supplemented with [35S]methionine after addition of the inducer. The proteins in the culture fluid were fractionated resulting in a radioactively pure 63-kDa protein and 30- and 89-kDa protein preparations with residual minor radioactive impurities. The secreted 89-kDa protein shared at least one characteristic with some interferon-induced cell-associated enzymes: it bound double-stranded RNA tightly. The 63-kDa protein was undetectable in the culture fluid from resting BALB/c-3T3 cells and was barely or not at all detectable in the culture fluids from growing BALB/c-3T3 and NIH 3T3 cells, respectively. The protein was, however, among the three major constitutively secreted proteins in the case of growing Kirsten murine sarcoma virus-transformed NIH 3T3 cells. Treatment with 1000 units/ml beta-interferon decreased the accumulation of the 63-kDa protein in the culture fluid of quiescent BALB/c-3T3 cells which had been treated with a platelet-derived growth factor preparation by over 80% and that in the culture fluid of Kirsten murine sarcoma virus-transformed NIH 3T3 cells by about 50%. This decrease was not a consequence of an inhibition of cell growth.
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PMID:Characteristics of 30-, 63-, and 89-kilodalton proteins whose secretion from mouse fibroblasts is altered by beta-interferon. 406 15

The simian sarcoma virus transformation-specific glycopeptide (SSV-TrSgp) represents a proteoglycan which is released from SSV-transformed cells and can be detected by an autologous goat serum against SSV nonproducer cells (SSV-NP serum) (H.-J. Thiel, R. Hafenrichter, and B. Gregor, 1984, Virology 134, 138-147). This antiserum has now been shown to react also with human platelet-derived growth factor (PDGF). Antiserum to PDGF precipitated a glycosylated molecule from the tissue culture supernatant of SSV-NP cells. The respective antigen was identified as the SSV-TrSgp (after immunoprecipitation including enzymatic treatment with chondroitinases). The anti-SSV-TrSgp reactivity of both the anti-PDGF serum and the SSV-NP serum could be absorbed by pure PDGF. Therefore, the SSV-TrSgp is apparently immunologically related to human PDGF. Additional studies indicated that the SSV-TrSgp protein backbone and PDGF have very similar molecular weights.
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PMID:Simian sarcoma virus transformation-specific glycopeptide: immunological relationship to human platelet-derived growth factor. 608 51

The oncogene of simian sarcoma virus, v-sis, encodes a protein which is homologous to human platelet-derived growth factor (PDGF). This v-sis-encoded protein was expressed in bacteria using an inducible promotor of lambda phage. Soluble extracts from these bacteria contained a substance which competed with 125I-PDGF for PDGF receptor sites in fibroblast membranes. The receptor competition activity was correlated with the presence of the v-sis-encoded protein as assessed by genetic and immunochemical criteria. These results directly demonstrate that the v-sis oncogene product is functionally related to PDGF.
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PMID:A v-sis oncogene protein produced in bacteria competes for platelet-derived growth factor binding to its receptor. 608 10

The platelet-derived growth factor (PDGF) has several well defined important biologic activities. Platelet-derived growth factor is the major mitogen in human serum for cells of mesenchymal origins; it is a potent chemoattractant protein for human monocytes, neutrophils, fibroblasts, and smooth muscle cells; and has been implicated in transformation by simian sarcoma virus and perhaps in transformation by other agents as well. In this article, PDGF has been shown to stimulate activation of human peripheral blood neutrophils defined by loss of membrane associated calcium as reflected by loss of chlortetracycline fluorescence, release of superoxide anion and specific granule enzymes, and enhanced neutrophil adherence and aggregation. These responses occurred in a dose-dependent fashion at concentrations of PDGF between 10 ng/mL (0.4 nmol/L) and 40 ng/mL (1.5 nmol/L) and were comparable to effects obtained with optimal concentrations of fMLP and C5a. Degranulation induced by PDGF was selective for secondary (specific) granules and not primary (azurophil) granules. Platelet-derived growth factor thus is ideally suited for a pivotal role in attracting inflammatory cells locally and initiating neutrophil activation at sites of blood vessel injury. Platelet-derived growth factor or a closely related protein also may play an important role in attracting and activating neutrophils in association with inflammatory tumors.
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PMID:Platelet-derived growth factor promotes polymorphonuclear leukocyte activation. 609 15


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