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

The expression and activities of epidermal growth factor (EGF) receptor and a highly related protein (Mr approximately 190,000 protein; p190) were characterized from a human glioma cell line, KE. p190 was specifically immunoprecipitated with a monoclonal antibody with specificity against the EGF receptor (Mr approximately 170,000; p170). Furthermore, both proteins were shown to possess tyrosine-protein kinase activities, although p170 required the presence of EGF to undergo autophosphorylation, whereas p190 appeared to be constitutively activated. Partial and total proteolytic polypeptide analyses of the two proteins suggested that their phosphopeptides were nearly identical and were phosphorylated on similar amino acid residues. However, a number of alterations were observed between [35S]methionine-labeled polypeptides of p170 and p190. This was also supported by the finding that the size of the protein cores of p170 and p190 was different. This observation is in agreement with Northern blot analysis in which KE cells expressed a novel EGF receptor RNA of 10.5 kilobases in addition to the previously reported 10-kilobase RNA. Southern blot analysis of the EGF receptor gene also revealed some amplification, approximately 4- to 5-fold; however, no significant rearrangements were noted in the KE cell DNA. These results suggest that p190 represents an endogeneous structurally and functionally altered EGF receptor.
 ...
PMID:Expression of an altered epidermal growth factor receptor by human glioblastoma cells. 341

The association of the src homology 2 (SH2) domain-containing tyrosine phosphatase (SH-PTP2) with the activated epidermal growth factor (EGF) and platelet-derived growth factor receptors, as well as the insulin receptor substrate 1 and growth-factor-receptor-bound protein 2 and its intrinsic tyrosine phosphatase activity suggests an important role for this phosphatase in signal transduction. Previous studies have shown a positive role for SH-PTP2 in growth-factor-mediated cell signaling. We show here that SH-PTP2 can also function to negatively regulate EGF-mediated signal transduction in the human glioma cell line SNB19. We demonstrate this by showing that, in SNB19 cells, which lack the ability to proliferate in response to EGF but retain the ability to bind EGF and also activate the EGF receptor as well as allow for the association of SH-PTP2 with the phosphorylated receptor, stable overexpression of an interfering SH-PTP2 mutant can restore the ability of these cells to proliferate in response to EGF.
 ...
PMID:An alternative role for the src-homology-domain-containing phosphotyrosine phosphatase (SH-PTP2) in regulating epidermal-growth-factor-dependent cell growth. 758 74

We have detected a tyrosine-phosphorylated 200-kDa protein in two human tumor cell lines, A1235 glioma and A172 glioblastoma. The protein is an integral plasma membrane sialoglycoprotein with tyrosine kinase activity. The interesting characteristic of this protein (gp200) is that it is recognized by a number of monoclonal and polyclonal antibodies to the 170-kDa epidermal-growth-factor (EGF) receptor; however, it lacks detectable EGF-binding activity. gp200 differs from three other EGF-receptor-related proteins, erb-B-2, erb-B-3 and erb-B-4 gene products, and hence appears to be yet another member of the EGF-receptor family of proteins. This is further strengthened by the fact that both gp200 and the EGF receptor contain a common epitope which is recognized by an anti-peptide IgG to the beta-type platelet-derived-growth-factor (PDGF) receptor. Our previous studies [Bishayee, S., Majumdar, S., Scher, C.D. & Khan, S. (1988) Mol. Cell. Biol. 8, 3696-3702] have demonstrated that this epitope in the PDGF receptor is highly susceptible to the phosphorylation state of the receptor and that such a conformational change appears to be important in biological message transmission. The expression of gp200, which appears to have tyrosine kinase activity and is immunologically related to the EGF receptor in tumor cells, suggests its possible involvement in cell growth.
 ...
PMID:Characterization of a novel epidermal-growth-factor-receptor-related 200-kDa tyrosine kinase in tumor cells. 760 Nov 58

The objective of the present study was to determine the frequency of amplifications of three different members of the erbB gene family in human glioblastoma multiforme (GBM). We investigated 47 glial tumors (37 GBM WHO grade IV, 5 anaplastic astrocytomas WHO III and 5 astrocytomas WHO II) by Southern and Western analysis, and immunocytochemistry. Gene amplification of erbB genes in human malignant gliomas was restricted to the EGF receptor (EGFR) gene, erbB-1. We found amplification of the EGFR gene in 49% (18/37) of GBM but not in the astrocytomas WHO II/III. The erbB-2 and erbB-3 genes showed no amplification in the tumor specimens investigated in this study. At the protein level we found overexpression of the EGF receptor in 86% (32/37) by Western analysis and in 92% (34/37) by immunocytochemistry. Expression of the ERBB2 protein was present in 54% (20/37) but immunoreactivity was much weaker than for EGF receptor and in most cases barely detectable by Western analysis and immunocytochemistry. The ERBB3 protein was not expressed in the glial tumors investigated in this study. Of the three erbB genes only gene amplification and overexpression of the EGF receptor seems to have an impact on tumor progression of human gliomas. Our data from immunohistochemistry indicate that ERBB2 expression in GBM is closely correlated with EGF receptor levels and is therefore not useful as an independent prognostic parameter.
 ...
PMID:Amplification and differential expression of members of the erbB-gene family in human glioblastoma. 776 96

The effects of tyrphostin, a selective protein tyrosine kinase inhibitor, on epidermal growth factor (EGF)-stimulated cell growth and EGF-receptor tyrosine kinase activity were studied in four human glioma cell lines. Stimulation by EGF induced variable enhancements of cell growth as well as tyrosine phosphorylation of EGF receptor and intracellular target proteins in all glioma cell lines. The level of immunoreactive EGF receptor detected with antibodies against extra- and intracellular domains was moderate in all four glioma cell lines, but markedly decreased with the latter antibody in two glioma cell lines. This variation was associated with considerable reduction of the EGF-stimulated tyrosine autophosphorylation level. Tyrphostin inhibited dose-dependently the EGF-stimulated cell growth and tyrosine autophosphorylation in all glioma cell lines, and the optimum time for the maximum inhibitory effect on tyrosine autophosphorylation was 12 to 18 hours after treatment with tyrphostin. The antiproliferative activity of tyrphostin nearly correlated quantitatively with its potency as an inhibitor of the EGF-stimulated EGF receptor tyrosine kinase activity. Tyrphostin had no significant effect on the immunoreactive EGF receptor levels, on the affinity constants and numbers of EGF receptor, or on the down-regulation and specific internalization of EGF receptor in any glioma cell line, suggesting that the effects of tyrphostin are not likely to be the results of reduction in EGF receptor and EGF binding capacity. In addition, the serum-stimulated cell growth was also inhibited dose-dependently by higher concentrations of tyrphostin in all glioma cell lines. It might be suggested, therefore, that tyrphostin inhibits EGF-stimulated cell growth by a specific suppression of EGF receptor tyrosine kinase activity, and at higher concentrations there appears to be some degree of either nonspecific inhibition or inhibition of serum-stimulated protein tyrosine kinase activity to induce the cell growth inhibition of gliomas.
 ...
PMID:Effect of tyrphostin on cell growth and tyrosine kinase activity of epidermal growth factor receptor in human gliomas. 805 49

Autocrine growth due to dysregulation of growth factor production may have a role in the development of neoplasia. We demonstrated that U251MG, a well characterized human malignant glioma cell line, had high affinity receptors for epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) by enzyme-linked immunosorbent assay. We assessed the inhibitory effect of anti-EGF receptor (EGFR), anti-FGF, and anti-PDGF monoclonal antibodies (MoAbs) on the growth of U251MG cells using the MTT assay and 3H thymidine uptake. At 50 micrograms/ml, the EGFR, FGF, and PDGF MoAbs significantly decreased cell numbers by 31.0%, 31.2%, and 31.0%, respectively, when compared to control cultures in the MTT assay. At the same concentration, the EGFR, FGF, and PDGF MoAbs reduced 3H thymidine uptake by 45.2%, 41.1%, and 40.0%, respectively, when compared to control cultures. At 50 micrograms/ml, a combination of the 3 MoAbs (16.6 micrograms/ml each) caused a 13.7% greater decrease in cell numbers in the MTT assay and an 11.9% greater decrease of 3H thymidine uptake. These findings suggest that the antigrowth factor MoAbs interrupted the autocrine loop at the growth factor receptor level. In conclusion, the demonstration that MoAbs directed against EGFR, FGF, and PDGF inhibit the growth of malignant glioma cells in vitro raises the possibility that these antibodies could be used clinically to treat malignant glioma either alone or conjugated to other agents.
 ...
PMID:[Growth control of a human glioma cell line by multiple autocrine loop blockade]. 816 53

The objective of our study was to determine the frequency of EGF-receptor-gene rearrangement in relation to tumour-growth behaviour in an unselected group of glioma patients. We investigated 73 glial tumours with different grades of malignancy (17 low-grade gliomas, 14 anaplastic variants, and 42 GBM) by Southern analysis, reverse transcriptase PCR (RT-PCR) amplification of mRNA, and Western analysis. An amplification of the EGF-receptor gene was present in 19/42 GBM but in only 1 anaplastic astrocytoma. By RT-PCR, 4/19 GBM with gene amplification showed a specific amino-terminal aberrant splice mutation of 801 bp in addition to undeleted mRNA. By Western analysis, 27/42 GBM showed expression of the EGF-receptor protein. Protein levels, however, varied among individual tumours. Four GBM containing an aberrant splice mutation exhibited an immunoreactive protein of 130 kDa MW in addition to the normal EGF-receptor protein p170. All GBM patients underwent surgery followed by a standard course of radiotherapy. Neuroradiological follow-up in 31/42 GBM patients consisted of bimonthly MRI examinations. There was a statistically significant difference in the mean latency period until tumour regrowth of patients suffering from GBM with and without EGF-receptor-gene amplification (9 weeks vs. 32 weeks). Our data indicate more rapid tumour regrowth kinetics of GBM with amplified EGF receptor genes in vivo.
 ...
PMID:Amplification of the epidermal-growth-factor-receptor gene correlates with different growth behaviour in human glioblastoma. 826 81

Genetic polymorphism of the epidermal growth factor (EGF) receptor gene following Taq I digestion was compared between samples of genomic DNA from glioma-derived cell lines and Caucasoid and Japanese subjects. The same three allelic forms of the EGF receptor gene, marked by variant fragments of approximately 12.8, 11.6 and 10.8 kb in size were common to both ethnic groups and the 12.8- and 11.6-kb fragments were found in the glioma-derived cell line DNA. A further variant fragment of approximately 13.8 kb in size has been shown to be thus far restricted to the Japanese. These data suggest that most allelic forms of the EGF receptor gene recognized by Taq I restriction fragment length polymorphism have a long evolutionary history and probably do not predispose to development of malignant glioma.
 ...
PMID:TaqI polymorphism of the epidermal growth factor receptor gene in Caucasoids and Japanese. 851 25

Neoplastic transformation occurs in all glial cell types of the human nervous system, producing a wide variety of clinico-pathological entities and morphological variants. Astrocytomas are most common and span an unusually wide spectrum, ranging from the slowly growing juvenile pilocytic astrocytoma to the highly malignant glioblastoma multiforme. Diffusely infiltrating astrocytomas of the cerebral hemispheres show an inherent tendency for progression towards a more malignant phenotype. This change is morphologically categorized in histologic grading schemes (e.g., WHO Grade II to IV) and is associated with the sequential acquisition of genetic alterations, including mutations in the p53 and homozygous deletions of the p16 tumour suppressor genes. Loss of heterozygosity on chromosomes 10 and 19q as well as amplification of the EGF receptor are largely restricted to malignant gliomas and thus considered late events in astrocytoma progression. Gliomas often show phenotypic expression of different glial cell lineages (e.g., oligoastrocytoma). Recent studies suggest that the occurrence of mixed gliomas is not indicative of a polyclonal origin but rather reflects altered gene expression, leading to a change in the balance of growth factors influencing glioma differentiation.
 ...
PMID:Histopathology, classification, and grading of gliomas. 858 58

The past few years have seen remarkable progress in understanding the molecular genetic basis of glioma formation. Affected oncogenes and tumor suppressor genes have been identified and putative tumor suppressor loci have been mapped. These studies have illustrated distinct molecular pathways for different glial neoplasms. We summarize the findings of an ongoing study initiated to characterize human gliomas on a molecular basis. The data are compiled from 150 astrocytic, oligodendroglial, and mixed gliomas that were assessed for genomic alterations characteristic of these neoplasms, i.e., loss of portions of chromosomes 1p, 9p, 10, 17p, 17q, and 19q, mutations of the p53 tumor suppressor gene, and amplification of the EGF receptor (EGFR) gene. Our findings support the hypothesis that distinct genetic pathways result in the formation of astrocytic and oligodendroglial neoplasms of different malignancy grades, and that glioblastoma multiforme may be subdivided into genetically distinct subsets. Such findings may not only lead to a better understanding of neoplastic transformation in glial cells, but may also have a major impact on clinical neuro-oncology.
 ...
PMID:Molecular pathways in the formation of gliomas. 858 67


<< Previous 1 2 3 4 5 6 7 8 9 Next >>