Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for the epidermal growth factor (EGF) receptor is amplified in a variety of neoplastic tissues, including malignant gliomas. To reveal whether increased sensitivity to EGF has significance for the supply of metabolic substrate to tumor cells, the rate of glucose transport was determined in cells exposed to EGF for up to six hours. In the epidermoid carcinoma line A431, and in primary cultures from 7/12 human glioma biopsies, EGF (10 ng/ml) induced an increase (two-fold) in glucose transport. This effect was transient and independent of protein synthesis.
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PMID:Epidermal growth factor induces glucose transport in primary cell cultures derived from human astrocytic glioma biopsies. 160 38

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.
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PMID:Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. 220 83

An extensive panel of monoclonal antibodies (MAb) and monospecific antisera reactive against neuroectodermal-, neuronal-, glial-, and lymphoid-associated antigens, extracellular matrix, HLA, and cell-surface receptors was used to characterize the phenotype of four continuous, karyotypically distinct medulloblastoma cell lines and transplantable xenografts. All four cell lines demonstrated significant reactivity with anti-neuroectodermal-associated MAb. No apparent pattern of reactivity with anti-lymphoid MAb was seen; notably, there was a uniform absence of detectable Thy-1. Review of the complete antibody reactivity profile revealed a dichotomy between lines TE-671 and Daoy and lines D283 Med and D341 Med, which have been previously shown to express neurofilament protein in culture and xenografts, and to exhibit neuroblastic morphological features in biopsy and xenograft tissue sections. TE-671 and Daoy reacted with the MAb directed against tenascin, epidermal growth factor (EGF) receptor, HLA-A,B epitopes, beta 2-microglobulin and 5/8 of the glioma-associated antigens, but did not react with the anti-neurofilament protein (NFP) MAb. D283 Med and D341 Med expressed NFP but did not react with MAb against tenascin, EGF receptor, HLA-A,B epitopes, beta 2-microglobulin or 6/8 and 7/8 (respectively) of the glioma-associated antigens. The observed phenotypic differences provide a conceptual framework for investigating basic differences in the biological behavior of medulloblastoma. Moreover, the subdivisions can be evaluated for prospective value in tissue diagnosis, cerebrospinal fluid cytology and antibody-mediated imaging and therapy.
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PMID:Phenotypic analysis of four human medulloblastoma cell lines and transplantable xenografts. 253 15

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

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.
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PMID:Expression of an altered epidermal growth factor receptor by human glioblastoma cells. 341

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.
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PMID:Amplification and differential expression of members of the erbB-gene family in human glioblastoma. 776 96

The neu/c-erbB-2 oncogene encodes a 185 kd transmembrane protein (p185). Here we have used the monoclonal antibody (mAb) 3B5 to determine the expression of p185 in a series of fixed biopsy specimens of 180 human brain tumors, including the most frequent entities and, in addition, 18 recurrent gliomas with malignant progression. In summary, 3B5 immunoreaction was most prominent in astrocytomas of different grades of malignancies and in meningiomas. In World Health Organization (WHO) grade II astrocytomas mab 3B5-immunoreaction was related to the cytomorphological phenotype. Fibrillary astrocytomas showed no or only a weak immunoreaction (four of five, 80%) in contrast with protoplasmic or gemistocytic astrocytomas, where a strong reaction was observed in most cases (six of nine, 66.6%, and four of five, 80%, respectively). In WHO grade II to WHO grade IV astrocytomas a trend towards higher scores with increasing grade was found. In a limited number of cases (18 gliomas and two meningiomas) of the tumor series tested other mAbs against neu/c-erbB-2 epitopes, especially the mabs 9G6 and CB11, gave qualitatively comparable results. In WHO grade I pilocytic astrocytomas a wide range of 3B5 immunoreactivity has been observed. The results of in situ hybridization using a 32P-labeled neu/erbB-2 RNA probe performed on four WHO grade I and II astrocytomas, seven WHO grade IV glioblastomas, one WHO grade II oligoastrocytoma, one WHO grade III anaplastic astrocytoma, and three WHO grade I meningiomas were consistent with these immunomorphological data, and Northern blot analysis also indicated an overexpression of neu/c-erbB-2 mRNA in gliomas of different grades of malignancy and in meningiomas. These elevated neu-erbB-2 transcript levels occurred in the absence of gene amplification. In a second series of recurrent gliomas with malignant progression (n = 18) the higher 3B5-immunoreaction scores were apparent in the more malignant recurrent gliomas. In this series the overexpression of neu/c-erbB-2 parallels glioma progression. In our cases it was not, however, correlated with the postoperative relapse-free interval or with the overall length of survival.
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PMID:Expression of neu/c-erbB-2 in human brain tumors. 791 8

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.
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PMID:TaqI polymorphism of the epidermal growth factor receptor gene in Caucasoids and Japanese. 851 25

A delivery molecule for directed boron neutron capture therapy against epidermal growth factor (EGF) receptor-rich tumors, such as gliomas, squamous carcinomas, and breast cancers, is presented. EGF and sulfhydryl boron hydride (BSH) were covalently coupled to an allylated 70 kDa dextran chain to form a conjugate. Conjugates with low and high substitution rates of BSH, as well as without BSH, were investigated. The conjugate with a low amount of boron had approximately 6 BSH (72 boron atoms) per dextran, while the conjugates with higher amounts had an average substitution of 55 BSH (660 boron atoms) per dextran. The maximum substitution of boron to dextran in a single experiment was over 800 boron atoms. Binding, retention, and internalization of 125I-labeled conjugates were investigated on cultured human glioma cells. Binding of the conjugates was EGF receptor specific, but the amount of BSH coupled to dextran affected specificity, more than the presence of dextran. The nonspecific binding of the conjugates increased with the amount of attached boron. This was partly due to nonspecific adhesion to the plastic in the culture dishes. [125I]EGF-allyldextran with 6 BSH had a binding maximum after 4 h of continuous incubation and thereafter decreased in binding, while [125I]EGF-allyldextran with the higher substitution rate had a slow increase of binding during 24 h. Over 93% of the radioactivity bound to the cells was internalized, but the retention was quite poor. Only one-third of the cell-bound activity was still associated to the cells 4 h after incubation had ended. In conclusion, it is possible to load the conjugates produced with high amounts of boron, and they retained specificity for the EGF receptor and internalized into cultured cells. Theoretical calculations show that about 10(3) boron atoms per EGF-based conjugate are needed to give a satisfactory therapeutic response. These conjugates are within reach of that level.
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PMID:Development and in vitro studies of epidermal growth factor-dextran conjugates for boron neutron capture therapy. 888 21

Little is known about the role of the N-linked oligosaccharides in the function of the epidermal growth factor (EGF) receptor (EGF-R). In a human glioma cell line, U373 MG, EGF-Rs contain the bisecting N-linked oligosaccharide sequence recognized by erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris (E-PHA). Incubation of E-PHA with cultured U373 MG cells results in inhibition of EGF binding to its receptor and consequently inhibition of EGF-induced autophosphorylation of the receptor. Consistent with the inhibitory effects on the EGF-R, phenotypic events that depend on EGF-R signaling, such as cell spreading and proliferation, were also found to be modified. The effect of this lectin seems to be specific because leukoagglutinating phytohemagglutinin lectin from P. vulgaris (L-PHA), an isolectin of E-PHA, had no effect on EGF-R activity or the biological functions of these cells even though L-PHA was able to bind to the EGF-R. These findings suggest the presence of an important bisecting N-linked oligosaccharide structure in close proximity to the EGF binding site on the receptor. Furthermore, these results suggest the possibility that E-PHA lectin binding may provide an additional approach to blocking EGF-dependent glioma cell growth.
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PMID:Binding of erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris to the epidermal growth factor receptor inhibits receptor function in the human glioma cell line, U373 MG. 893 57


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