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)

Insulin and insulin-like growth factors are neuroactive peptides. We investigated the effect of insulin-like growth factor I (IGF-I) on Ca2+ channel currents in 108CC15 neuroblastoma x glioma (N x G) cells and a possible role of protein kinase C (PKC). Whereas the native IGF-I enhanced the Ca2+ channel current density in N x G cells, the boiled IGF-I had no effect. The effect of IGF-I occurred after 1-2 h incubation and reversed within 24 h. Ca2+ channel currents recorded in control cells were mainly of a low-threshold fast inactivating type and showed a mean density of 5.9 +/- 0.3 pA/pF. Current density in cells incubated with IGF-I (0.2 micrograms/ml) for 2 h increased to 9.2 +/- 0.8 pA/pF. Ca2+ channel currents in cells treated with IGF-I showed an enhanced amount of a high-threshold slowly inactivating Ca2+ current type sensitive to the dihydropyridine isradipine and the snail toxin omega-conotoxin. The effect of IGF-I was suppressed by coincubation with the PKC inhibitors 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) and staurosporin which were both without effect on current density in control cells. Whereas the inactive phorbol ester phorbol 12-myristate 13-acetate (PMA) failed to modulate Ca2+ channels in N x G cells, stimulation of PKC by the active phorbol ester PMA mimicked the effect of IGF-I. The effects of IGF-I and phorbol ester were not additive. Our data suggest an intracellular mechanism dependent on PKC and we propose a physiological relevance of the observed Ca2+ channel modulation by IGF-I in the neuroactivity of the peptide.
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PMID:Insulin-like growth factor I modulates voltage-dependent Ca2+ channels in neuronal cells. 133 4

Growths factors, defined as polypeptides that stimulate cell proliferation, are major growth-regulatory molecules for cells in culture and probably also for cells in vivo. Evidence has been derived for autocrine system in which the cell produces its own growth factor. Several growth factors as well as their cellular receptors have been identified as productions of proto-oncogenes. Furthermore, these growth factors have been identified as mitogens in tumors of the central nervous system. The roles of growth factors including platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and its receptor. Insulin-like growth factors (IGFs), transforming growth factors (TGFs) and fibroblast growth factor (FGF) on the proliferation of brain tumors, especially glioma were reviewed. The activation of cellular proto-oncogenes resulting in the autocrine system of growth factors and their receptors offers the opportunity for therapeutic interference. Therapeutic efforts will be based on the concepts of neutralization of growth factors, antagonizing growth factors at their receptors, irreversibly blocking receptors, and interference with oncogene product synthesis. Specific antibody for growth factors or receptors will be able to inhibit the proliferation. Trapidil, an antagonist for PDGF, can inhibit the proliferation of a PDGF-producing glioma cell. We can assume that the further analysis of growth regulatory mechanism will allow the design of new therapeutic approaches.
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PMID:[Microbiological approach to the treatment of brain tumors]. 199 13

Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I.
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PMID:Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. 199 66

Insulin and insulin-like growth factors (IGFs) are anabolic effectors in many tissues and cultured cells, including astrocytes and neurons. Receptors for insulin and IGFs are found throughout the human brain. We examined the level of insulin and IGF receptors on membranes prepared from surgical specimens of tumor (astrocytomas and glioblastomas) and normal human brain. Specific binding (per 100 micrograms membrane protein) of insulin was less than 5% in all normal and tumor samples. Specific binding of IGF-I to 12 normal brain specimens ranged from 1-8%. IGF-I binding to 18 glioma specimens ranged from 2-25%. Scatchard analyses of IGF-I binding confirmed increased IGF-I-binding sites in some glial tumors vs. normal brain, but detected no difference in affinity characteristics. Cross-linking of [125I]IGF-I demonstrated that glioma tissue expressed the same lower mol wt (approximately 118 kDa) alpha-subunit as the normal brain confirming the neural origin of the cells expressing the IGF-I receptor. IGF-binding proteins (approximately 40 kDa) were also found in the membranes of some of the glioma but none of the normal brain specimens. In cell lines derived from glioma specimens, IGF binding was readily detectable (4-10% specific binding), but insulin binding was barely detectable (0-03%) in every line examined. The size of the IGF-I alpha-subunit in the cultured cells was larger (approximately 133 kDa) than that in the original tissue. Most glioma cell lines exhibited an IGF-I dose-dependent stimulation of thymidine incorporation into DNA, and partially purified IGF-I receptors from these cells exhibited a dose-dependent stimulation of the autophosphorylation of the beta-subunit. We conclude that human glioma cells have functional IGF-I receptors and suggest a role for this receptor in glioma cell growth.
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PMID:Insulin-like growth factor-I receptors in human glial tumors. 216 27

We have measured insulin and insulin-like growth factor I (IGF-I) binding in human gliomas, meningiomas, and normal brain and studied the effect of insulin on the morphology, proliferation, and differentiation of central nervous system tumor and normal fetal cells in culture. Specific 125I-insulin and 125I-IGF-I binding was demonstrated by competition-inhibition binding assays. Insulin binding was measured in plasma membrane preparations from 9 freshly isolated human meningiomas, 4 glioblastomas multiforme (GBMs), a low-grade glioma, a normal adult brain, and a fetal brain. IGF-I binding was measured in similar preparations from 5 meningiomas, 4 GBMs, a low-grade glioma, and a normal adult brain. Incubations were carried out at 4 degrees C for 18 to 20 hours. Meningiomas showed higher specific insulin binding per 0.25 mg of protein than GBMs (19% versus 3%, P less than 0.005), and this difference was not related to small differences observed in insulin degradation. By contrast, IGF-I binding was significantly higher in gliomas than in meningiomas (27% versus 12%, P less than 0.05). Also, IGF-I binding was significantly higher than insulin binding in GBMs (27% versus 3%, P less than 0.03); binding of both IGF and insulin was high in meningiomas. In normal adult brain IGF-I and insulin binding was 7 to 10%. The ability of insulin to support and enhance the growth of central nervous system tumor cells in culture was investigated. Cell cultures were derived from a freshly isolated glioblastoma, a low-grade glioma, and 3 meningiomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin and insulin-like growth factor I in brain tumors: binding and in vitro effects. 254 92

Insulin-like growth factors (IGFs) I and II are homologous peptides, which stimulate growth of several vertebrate tissues. Expression of IGF I and IGF II genes and production of IGFs have recently been demonstrated in rat and human brain. In search for the function of IGF I and IGF II in the central nervous system, we have studied IGF receptors in fetal and adult mammalian brain and growth effects of IGFs on primary cultures of fetal rat astrocytes. Two types of IGF receptor are present on adult rat brain cortical plasma membranes, on fetal rat astrocytes and on human glioma cells. Type I IGF receptor is composed of 2 types of subunits: alpha-subunits which bind IGF I and IGF II with high affinity and insulin weakly, and beta-subunits which show tyrosine kinase activity and autophosphorylation stimulated by IGF I and IGF II with almost similar potency. The molecular size of the type I IGF receptor alpha-subunit is larger in cultured fetal rat astrocytes and human glioma cells than in normal adult brain (Mr 130,000 versus 115,000), whereas the beta-subunit has the same electrophoretic mobility (Mr 94,000). The type II IGF receptor is a monomeric protein (Mr 250,000), which binds IGF II 5 times better than IGF I, and does not recognize insulin. The amounts of type II IGF receptor are significantly higher in fetal and malignant cells than in adult brain. Based on these findings we suggest that IGF receptors in brain undergo changes during fetal development and malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptors for insulin-like growth factors in the central nervous system: structure and function. 297 1

The existence of insulin receptors and biological responses to insulin on macromolecular synthesis have been studied in C6 glioma cells. Binding of 125I-insulin to C6 glioma cells was specific, time- and PH-dependent. Porcine insulin competed for 125I-insulin binding in a dose-dependent manner. Unlabeled polypeptides, including glucagon, bovine growth hormone, bovine prolactin did not compete for 125I-insulin binding. Scatchard analysis of the binding data gave a curvilinear plot which may indicate negative co-operativity or the existence of both high and low affinity (Ka = 7.55 x 10(10) - 4.25 x 10(9] sites. Incubation of cultures with insulin caused a time and dose-dependent stimulation of DNA, RNA and protein synthesis in C6 glioma cells (measured by 3H-thymidine, 3H-uridine or 3H-leucine incorporation into DNA, RNA, or protein respectively). The increase of macromolecular synthesis was admitted at more than 2 nM concentration of insulin. Maximal stimulation of DNA synthesis (142% of control) occurred 6 hours after incubation with 167 nM insulin. The same concentration of insulin caused a 45% increase in 1 hour on RNA synthesis, a 37% increase in 2 hour on protein synthesis. These results indicate that C6 glioma cells have specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis. Insulin in the brain and even blood may be an important growth factor in the glioma cells of the patients with disrupted blood-brain-barrier.
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PMID:Insulin binds to specific receptors and stimulates macromolecular synthesis in C6 glioma cells. 304 34

Typical insulin receptors are present on neuroblastoma cell lines. High affinity binding for insulin was present in membrane preparations from NG108 (a hybrid mouse neuroblastoma-rat glioma) as well as in membranes from SK-N-MC and SK-N-SH, two human neuroblastoma cell lines. Specific [125I]insulin binding was 24.4% for NG108, 16.9% for SK-N-MC and 5.2% for SK-N-SH at membrane protein concentrations of 0.4 mg/ml. IC50 for [125I]insulin binding was 3.4 nM in NG108 membrane preparations and 0.9 nM for SK-N-SH and 1.8 nM in SK-N-MC membranes. Apparent mol. wt. for the alpha subunits (identified by specific immunoprecipitation using the anti-insulin receptor antiserum B10) on SDS PAGE was 134 kDa for NG108; 124 kDa for SK-N-MC and 120 kDa for SK-N-SH. Neuraminidase digestion increased the mobility of the alpha subunit from both NG108 and SK-N-MC receptors to 120 kDa, whereas that from SK-N-SH were unaffected. Endoglycosidase H and endoglycosidase F digestions increased the mobility of the alpha subunits of all 3 cell lines to varying degrees, suggesting the presence of N-linked glycosylation. Insulin induced autophosphorylation of the insulin receptor beta subunit in WGA-purified membranes from all 3 cell lines. In addition, phosphorylation of a protein with an apparent mol. wt. 105 kDa was stimulated by insulin in WGA purified membranes from NG108. Tyrosine-specific kinase activity was present in the membranes from each cell line and was stimulated by insulin in a dose-dependent manner from 10(-9) to 10(-6) M. Proinsulin was about 100 times less potent in stimulating phosphorylation of the artificial substrate poly (Glu, Tyr)4:1 when compared to insulin in accordance with its lower binding affinity to the insulin receptor. Hexose transport was stimulated by insulin in all 3 cell lines. These results indicate that neuroblastoma cells contain specific insulin receptors and that they may be useful as models for studying the role of insulin in nervous tissue.
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PMID:Characterization of the altered oligosaccharide composition of the insulin receptor on neural-derived cells. 335 62

Insulin receptors were detected in a variety of rat neuroblastoma and glioma cell lines. The binding of 125I-insulin to B103 neuroblastoma cells had characteristics typical of insulin receptors in other tissues, including high affinity for insulin, low affinity for insulin-like growth factor I (IGF-I), and curvilinear Scatchard plots. Using photoaffinity labeling procedures and sodium dodecyl sulfate (SDS) gel electrophoresis to analyze the subunit structure of insulin receptors in B103 cells, the predominantly labeled protein had an apparent molecular weight of 125K and the mobility of this protein was shifted after removal of sialic acid residues. On the basis of size and susceptibility to neuraminidase, the insulin binding subunit in neuroblastoma cells was identical to the alpha-subunit of insulin receptors in adipocytes and different from the 115K subunit found in brain. The presence of an "adipocyte" form of the insulin receptor in clonal cells derived from brain is probably a consequence of transformation and results from more extensive oligosaccharide processing of the 115K receptor expressed in normal brain cells. The fully glycosylated receptors in neuroblastoma cells were capable of exerting functions typical of insulin receptors in adipocytes such as internalization of insulin and stimulation of glucose transport.
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PMID:Structural and functional characteristics of insulin receptors in rat neuroblastoma cells. 390 Feb 95

Current treatment for disseminated prostate cancer, whether progressive or hormone-resistant, do not improve survival. Insulin growth factors (IGFs) are potent stimulants of prostate epithelial cells growth, their presence having been demonstrated in high quantities in several tumours such as lung, hepatoma, pheochromocytoma, malignant glioma and breast cancer. Local management of growth factors production could improve the results of second line therapy in hormone-resistant prostate cancer. Levels of IGF-I were determined by radioimmunoassay (RIA) in normal (n = 5), hyperplastic (n = 5) and tumoral (n = 8) prostate tissue. Presence of IGF-I is confirmed in all tissues (9.62 +/- 5.81; 8.32 +/- 7.81 and 6.02 +/- 1.42 ng/mg protein, respectively) but no significant differences are displayed among the three groups.
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PMID:[Insulin growth factor I (IGF-I) in normal, hyperplastic, and tumor prostatic tissue]. 876 97


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