Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the EGF-receptor gene is associated with the malignant nature of some tumors. We have recently reported the establishment of a human carcinoma cell line (T-CAR1), derived from a brain metastasis, that had 7 million EGF receptors per cell and was growth inhibited by EGF. The present study was carried out in order to further characterize the EGF-receptor protein in T-CAR1 cells, and to see if the overexpression of the EGF-receptor gene in these cells was associated with abnormalities at the genomic level. We have compared the T-CAR1 cells with the human glioblastoma cell line T-MG1, which has 135,000 EGF-receptors and is growth stimulated by EGF. The MW of the EGF receptors in T-CAR1 cells and T-MG1 cells was estimated to be 170 kDa, equal to the normal EGF-receptor. However, in T-CAR1 cells an additional protein reacted with the monoclonal antibody directed against the internal domain of the EGF receptor. The levels of EGF receptor-related RNAs in T-CAR1 cells and T-MG1 cells reflected the number of EGF receptors in these cell lines. The EGF-receptor gene was amplified ten-fold in T-CAR1 cells, while it was not amplified in T-MG1 cells. No restriction fragment length polymorphism of DNA digested with various restriction enzymes was seen in either of the cell lines. Chromosomal analysis of T-CAR1 cells showed polysomy of chromosome 7 and marker chromosomes derived partly from chromosome 7. Thus, in the T-CAR1 cell line it was an association between polysomy of chromosome 7 and EGF-receptor gene amplification.
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PMID:Polysomy of chromosome 7 is associated with amplification and overexpression of the EGF-receptor gene in a human carcinoma cell line derived from a brain metastasis. 170 Oct 94

Two transplantable cell lines of human glioblastoma multiforme GL-3 and GL-5 carried an amplification and overexpression of structurally altered epidermal growth factor (EGF) receptor gene: the 140 kilodalton EGF receptors in these cases exhibited a constitutively expressed tyrosine kinase activity without the ligand. Here, we isolated the abnormal EGF receptor cDNA from GL-5 cell line, and demonstrated that this cDNA bears a single large intramolecular deletion mutation 801 base pairs long within the ligand binding domain of EGF receptor. In other regions no amino acid substitution was observed. At the level of genomic DNA, this deletion appeared to start from the 1st intron and terminate in the 6th intron of the EGF receptor gene. However, in the two lines of glioblastoma, GL-3 and GL-5, the positions of the start or the end of the deletion mutation in these introns were not identical, suggesting an involvement of a unique recombination mechanism in the formation of deletion mutation. A weak but ligand-independent transforming activity was observed in the deletion-carrying EGF receptor cDNA.
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PMID:A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors. 216 66

Synthesis and metabolism of the epidermal growth factor (EGF) receptor are extensively regulated to modulate cellular responses to ligand. To study regulation of EGF receptor gene expression, the 5' region of the gene was isolated from a human placental genomic library. A 5' proximal 1.1-kilobase fragment (-1100 to -19 relative to the ATG translation start site) and subfragments of this were subcloned in both forward and reverse orientations into the luciferase expression vector pSVOAL delta 5' and transfected into human cell lines. Luciferase activity was stimulated by treatment of transfected HeLa cells with EGF, 12-O-tetradecanoylphorbol 13-acetate (TPA), (Bu)2 cAMP, retinoic acid, and dexamethasone. Deletion analysis indicated full retention of activity after removal of the -1100 to -485 region (-485 to -19 fragment), but a 5-fold reduction in activity on removal of the -485 to -153 region (-153 to -19 fragment). Despite a reduction in basal activity, the proximal 134-basepair fragment retained responses to all inducers. Additivity was observed in response to maximal concentrations of TPA plus retinoic acid and of TPA plus (Bu)2 cAMP; the response to a combination of four inducers exceeded that to the RSV-LTR strong promoter. Differences in stimulated responses were observed in various recipients, with hepatoma HepG2 cells lacking responses to (Bu)2 cAMP and glioblastoma T98G cells lacking responses to EGF and TPA. These results indicate that a 134-basepair DNA fragment closely adjacent to the translation start site contains elements responsible for directing basal and stimulated expression of the EGF receptor gene.
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PMID:Regulation of epidermal growth factor receptor gene expression. 254 Apr 31

Distribution of the epidermal growth factor (EGF) receptor in the surgical specimen of the human glioma was studied by immunohistochemical techniques using a monoclonal anti-EGF receptor antibody. Of 11 gliomas examined, EGF receptors were detected in nine glioblastomas and in one fibrillary astrocytoma. In the majority of cells, staining was observed over the cell membrane. Nuclear and cytoplasmic staining was also seen. In four glioblastomas, EGF receptor-positive cells were diffusely distributed in the tumor tissue. In one glioblastoma and one fibrillary astrocytoma, only a few positive cells were observed. These results imply the possible role of EGF receptors in the cellular proliferation of the human glioma.
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PMID:Epidermal growth factor receptor in human glioma. 271 19

Two established human tumor cell lines, epidermoid carcinoma line A431 and glioblastoma line SF268, were studied to compare the interaction of each with epidermal growth factor (EGF). SF268 cells bound [125I] EGF with 35-40 fold higher affinity than did the A431 cells. The EGF binding sites of both lines were photoaffinity labeled using 2,4-NAPS-[125I] EGF, a photoreactive derivative of EGF. Extracts of photolysed cells analyzed by SDS-PAGE showed a difference between the two cell lines in the high molecular weight component corresponding to the EGF receptor. EGF in a dose range from 0.3-200 nM had no effect on thymidine incorporation by SF268 cells, whereas thymidine incorporation by A431 cells was markedly inhibited by EGF.
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PMID:Epidermal growth factor receptors in the human glioblastoma cell line SF268 differ from those in epidermoid carcinoma cell line A431. 299 56

The cell surface receptor for the mitogenic peptide epidermal growth factor (EGF) is involved in control of normal cell growth and may play a role in the genesis of human neoplasia such as squamous carcinoma and glioblastoma. Soft-agar growth and focus-formation experiments with NIH 3T3 mouse fibroblasts transfected with an expression plasmid demonstrated the ligand-dependent transforming potential of the human EGF receptor without structural alterations. Activation of overexpressed normal receptor alone appears to be sufficient for transformation of NIH 3T3 cells in vitro.
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PMID:Ligand activation of overexpressed epidermal growth factor receptors transforms NIH 3T3 mouse fibroblasts. 325 24

The binding capacity for epidermal growth factor (EGF) was determined in 34 intracranial neoplasms (14 glioblastoma, seven low-grade gliomas, six meningiomas, and seven others) and four specimens of normal brain by using [I125]EGF. EGF binding and binding affinity of the sites in the tumour and brain samples were compared to placenta and rat liver. All specimens of normal brain were negative. Ten of 14 glioblastoma specimens contained EGF binding (level range 10-39,660 fmol/mg protein), however, ligand binding affinity was high in only three tumours. Only one of nine low-grade gliomas contained EGF binding activity. Five of six meningiomas contained EGF binding sites (level range 49-776 fmol/mg protein) and binding affinity was high in two. When present EGF binding activity was found in all cellular fractions except the cytosol. There were no clinical or histopathological features within major tumour groups that were predictive of either high or specific EGF binding activity. These preliminary studies have confirmed that EGF receptor-like activity is present in the particulate fractions of intracranial neoplasms of both mesenchymal and neuroctodermal origin. In a large proportion of these tumours the EGF binding affinity is low, suggesting either a less specific or truncated EGF binding site.
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PMID:Epidermal growth factor binding in intracranial neoplasms: preliminary biochemical and clinicopathological findings. 326 5

By using Southern blot analysis, we found that in two cases of human glioblastoma multiforme, cells carried amplified c-erbB genes which bore short deletion mutations within the ligand-binding domain of the epidermal growth factor (EGF) receptor. The products of these mutated c-erbB genes were about 30 kilodalton (kDa) smaller than the normal 170-kDa EGF receptor, and the tumor cell membrane fractions containing the 140-kDa abnormal EGF receptor showed a significant elevation of tyrosine kinase activity without its ligand. In view of the similarity to the activated viral and cellular erbB genes in the avian system, these mutated and overexpressed EGF receptors might play a role in the onset or development of human glioblastoma cells.
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PMID:Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. 338 99

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.
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PMID:Characterization of a novel epidermal-growth-factor-receptor-related 200-kDa tyrosine kinase in tumor cells. 760 Nov 58

The epidermal growth factor (EGF) receptor is a membrane bound tyrosine kinase whose activity is initiated by ligand binding. The malignant brain tumour glioblastoma frequently shows amplification and rearrangements of the EGF receptor gene that are associated with the synthesis of a constitutively activated tyrosine kinase, lacking amino acids 6-273 near the protein's N-terminus. When expressed in Chinese hamster ovary (CHO) cells, this mutant receptor (p140EGFR) displays ligand-independent tyrosine kinase activity, stimulates DNA synthesis, and promotes cell proliferation. Here, we investigate the subcellular location of p140EGFR in CHO cell transfectants as well as in human glioblastoma tumours. p140EGFR had an intracellular location that contrasted sharply with the plasma membrane location of the wild-type EGF receptor. Endoglycosidase H sensitivity analysis and the pattern of p140EGFR immunoreactivity suggested that the aberrant tyrosine kinase resided primarily in the endoplasmic reticulum. The half-life of p140EGFR in the endoplasmic reticulum was extended several-fold over that of the ligand-activated wild-type receptor. The altered subcellular location of p140EGFR in combination with its prolonged half-life suggest that this activated tyrosine kinase may escape the regulatory mechanisms utilized for the attenuation of wild-type receptor signaling. Therefore, the previously reported growth stimulatory property of the ligand-independent p140EGFR may be attributed to a sustained tyrosine kinase activity resulting from an altered subcellular location.
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PMID:Altered subcellular location of an activated and tumour-associated epidermal growth factor receptor. 773 99


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