Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein encoded by the proto-oncogene c-sis is over-amplified in human neuroglial tumors and has been hypothesized as playing an important role in tumorigenesis, but this hypothesis remains to be clarified. In order to address this issue, we examined the effect of 18-bp oligodeoxynucleotides complementary to the sense mRNA of c-sis upon glioma cell growth. First, we investigated the expression of c-sis protooncogenes within cultured human glioma cell lines and also fresh glioma specimens by using polymerase chain reaction. We could detect mRNA transcripts of c-sis in 3 out of 4 glioma cell lines (U138MG, U251MG and A172) and two in 5 glioblastoma multiforme specimens. The antisense oligonucleotides complementary to c-sis mRNA were efficiently incorporated into A172 in vitro and the kinetic study showed that maximum uptake occurred after 48 hours of incubation with antisense oligomers. Exposure of human glioma cell lines to antisense oligodeoxynucleotides targeted against first initiation codon inhibited cell proliferation in a time and dose dependent fashion. From the flow cytometric analysis using anti-c-sis sera, it was demonstrated that the antisense oligomers specifically block the de novo synthesis of intracellular c-sis protein by glioma cells dose-dependently. In contrast to this, the corresponding sense oligomers inhibited neither synthesis of c-sis protein nor glioma cell growth. Taken together, these results clearly support a role of c-sis protein in the proliferation process and show that inducible protein expression can be blocked by means of synthetic oligonucleotides complementary to a coding exon.
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PMID:[Inhibition of c-sis protein synthesis and cell growth with antisense oligonucleotides in human glioma cells]. 150 12

Sodium butyrate has been shown to inhibit the growth and induce the differentiation of F-98 rat glioma cells. In agreement with the morphological changes, we have found that mRNAs for fibronectin and collagen in these cells could be reversibly induced by butyrate. While Ki-ras mRNA levels remained relatively unchanged, mRNAs for fos and sis increased significantly during the course of butyrate induced differentiation. c-fos induction can be detected 30 min after butyrate addition, a peak level (greater than 20 fold) was reached at 2 h, with a subsequent gradual decline. c-sis induction was detectable 24 h after butyrate exposure, at which time the cells have assumed morphological transition. Interestingly, the sis mRNA induction was not reversible upon butyrate withdrawal. The sis mRNA half-life increased from 40 min in the untreated cells to 100 min in the butyrate induced cells indicating that the increase in the stability of sis mRNA contributed, at least in part, to the elevated levels of sis expression. These findings demonstrate a coordinated induction of fibronectin and collagen genes in the butyrate-treated F-98 cells. In addition, fos and sis transcripts were differentially induced; a rapid and transient induction of fos followed by an irreversible induction of sis at a later stage of differentiation.
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PMID:Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation. 210 2

Formal proof for an involvement of autocrine stimulation in the disturbed growth of malignant cells has been difficult to obtain, in part due to lack of precise methods of assessing growth factor production and receptor occurrence. In this study we have analyzed the mRNA levels for two growth factors and the corresponding receptors in a number of established human malignant glioma cell lines. Twenty-one tested lines all contained transcripts for the platelet-derived growth factor (PDGF) A chain while 16-17 of 21 expressed the c-sis/PDGF B chain gene; these two genes were expressed independently of each other. PDGF receptor transcripts were present in 15-16 of the 21 lines. Transcripts for the epidermal growth factor receptor were found in all 15 tested lines, in 2 of them at high levels, and the corresponding ligand transforming growth factor-alpha was found in 11 of 15 lines. No amplification or structural rearrangements of the genes, as analyzed by Southern blot hybridization, could explain the varying expression of PDGF A and B chain transcripts or the elevated levels of epidermal growth factor receptor mRNA. A correlation was found between cell morphology and expression of growth factor and receptor mRNA in these lines. The highest amount of PDGF receptor transcripts was found in cells with fibroblast-like morphology, and c-sis/B chain transcripts were found in small cell types and in cells with astrocyte-like morphology, while no clear relationship was found between PDGF receptor and A chain transcript levels or between morphology and A chain transcripts. It is possible that the findings reflect a coordinated expression of these genes in the progenitor cells. In conclusion, the data imply the existence of two possible autocrine loops in human malignant glioma lines, affecting the PDGF and epidermal growth factor receptor pathways.
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PMID:Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-alpha and their receptors in human malignant glioma cell lines. 245 31

A human malignant glioma cell line, U-251 Mg, cultured under serum free conditions, was shown to produce a growth factor for BALB/c 3T3 cells (glioma-derived growth factor-1, GDGF-1). The biological activity of GDGF-1 resided in a heat- and acid-resistant protein with a molecular weight (MW) of 25 kDa estimated by gel permeation chromatography. GDGF-1 activity was neutralized by a goat anti-human platelet derived growth factor (PDGF) antibody, indicating that the two factors were immunologically related. Furthermore, U-251 Mg cells constitutively expressed c-sis mRNA. When U-251 Mg cells were stimulated with bacterial lipopolysaccharide, 2 novel growth factors (GDGF-2 and GDGF-3) were produced in addition to the PDGF-like substance. GDGF-2 was determined to be greater than 100 kDa MW and was not neutralized by the goat anti-PDGF antiserum. The biological activity of GDGF-3 was also heat- and acid-resistant with an apparent 14 kDa MW. This factor also did not show any common antigenicity with PDGF. GDGF-2 and GDGF-3 are currently under investigation and evidence as to their natures will be published elsewhere. Our findings with this glioma cell line provide further evidence that inappropriate expression of growth factor-related genes could play important autocrine role(s) in the processes leading to malignant transformation and/or uncontrolled proliferation and may provide a paracrine stimulus for such processes as glioma neovascularization.
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PMID:Growth factors derived from a human malignant glioma cell line, U-251MG. 247 9

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

Expression of the c-sis oncogene, the gene encoding the B chain of platelet-derived growth factor (PDGF), may be related to initiation and/or progression of glial cell tumorigenesis by PDGF-mediated autocrine growth stimulation. As the mechanism for activation of expression of the c-sis gene in gliomas is not known, we searched for possible structural alterations of c-sis DNA in these tumors. Genomic Southern blots of DNA from 7 different cultured human glioblastoma cell lines and 15 different solid human brain tumors revealed no significant change in either the gross structure or the copy number of the c-sis gene in tumor cells vs. control cells. Activation of glioma c-sis gene expression is therefore not the result of a gross rearrangement or amplification of the c-sis gene. Expression of c-sis mRNA was detected in all of 12 different solid human brain tumors, 11 of which were of glial cell origin. However, in tissue adjacent to 5 different tumors, approximately the same level of c-sis mRNA was seen.
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PMID:Major structural alterations of the c-sis gene are not observed in a series of tumors of the human central nervous system. 258 29

Previously reported studies have suggested that variations in the pattern of proto-oncogene expression within a specific tumor type may denote an underlying difference in the biology and clinical behavior of those tumors. To more sensitively characterize malignant tumors of the central nervous system, we have used Northern blot hybridization analysis to determine the patterns of expression of seven proto-oncogenes in 20 cell lines established from biopsy specimens of patients with malignant glioma. The following proto-oncogenes are expressed at detectable levels in 30 micrograms of total RNA from most glioma cell lines examined: c-myc (20/20), c-mil/raf-1 (18/18), neu (19/20), c-erbB (19/20), and c-myb (17/20). In contrast, only half of the cell lines expressed detectable c-sis (10/20). In none of the cell lines tested was N-myc (0/20) mRNA detected. Morphologic analysis of these 20 cell lines revealed three different growth patterns: bipolar, epithelial, and pleomorphic-glial. Detectable levels of c-sis mRNA typically occurred with either an epithelial or pleomorphic-glial morphology. The pleomorphic-glial subgroup was also characterized by the expression of glial fibrillary acidic protein.
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PMID:Patterns of proto-oncogene expression in human glioma cell lines. 281 Mar 98

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

A cell line (NCE-G28) was established from the biopsy material of a human gliosarcoma of low histological differentiation. The initial cultures showed a mixed population of cells which in later stages became more uniform due to loss of slower growing constituents. The cells have been growing steadily for 20 months. A suspension of NCE-G28 cells injected s.c. as well as i.p. into nude mice produced solid tumors in all cases. Histologically these tumors closely resembled the original tumor. The original tumor, the nude mouse tumor, and NCE-G28 cells were immunochemically positive for glial fibrillary acidic protein as well as for neural plasma membrane antigen A2B5 expression. Two cell strains, 9B2C and 9B2E, were obtained by cloning of the initial cultures and another strain, NCE-G28T, was derived after explantation of a mouse heterotransplant. The two subclones were negative for glial fibrillary acidic protein expression but stained for cell surface fibronectin. NCE-G28T cells initially were positive for glial fibrillary acidic protein but lost this property within 8 months of cultivation. Karyotype analysis of NCE-G28 and the three strains revealed hyperdiploidy and six structurally altered marker chromosomes five of which were shared by nearly all cells. Receptors for epidermal growth factor were detected in all cell lines with the highest levels (about 300,000 receptors/cell) in the parental cell line. The epidermal growth factor receptors had an affinity of 2.5 nM (Kd) and by affinity cross-linking analysis a molecular weight of 170,000 was found. Initially, NCE-G28 cells responded to epidermal growth factor as well as fibroblast growth factor with increased rates of proliferation, while platelet derived growth factor had no effect. In higher passages the growth factor sensitivity was reduced. Using antibodies directed against synthetic protooncogene peptides the production of c-sis immunoreactive material was detected. NCE-G28 cells produce an autocrine factor which stimulated proliferation. This factor is present in conditioned medium and is active on cultured meningiomas and other glioma cell lines. NCE-G28 cells can be maintained in serum-free defined medium on plastic coated with fibronectin or an extracellular matrix from bovine corneal endothelial cells. The NCE-G28 cell line with its strains provide an in vitro model system in which the complexity of gliosarcoma cell populations and the interaction of the cloned cellular constituents can be studied.
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PMID:Biological and karyotypic characterization of a new cell line derived from human gliosarcoma. 327

Long-term culturing of brain cells from neonatal BD-IX rats after transplacental treatment with N-ethyl-N-nitrosourea (ENU) results in malignantly transformed cells after a lag period of about 250 days. During culturing, the brain cells undergo a sequence of morphological changes. We examined oncogene expression in cultured cells from ENU-treated animals and found that transformed glioma cells differ from premalignant glial cells by containing high levels of c-sis transcripts. We also report that the transformed cells synthesize functional platelet-derived growth factor. Because glial cells have receptors for platelet-derived growth factor, we propose that an autocrine mechanism plays an important role in ENU-induced brain tumorigenesis.
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PMID:Expression of c-sis and platelet-derived growth factor in in vitro-transformed glioma cells from rat brain tissue transplacentally treated with ethylnitrosourea. 354 May 93


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