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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here I discuss quantitative and qualitative activation of several receptor-type molecules in tumor cells. Recently we have shown that EGF-R gene is frequently mutated in human glioblastoma. Mutant EGF-R had a 801-bp deletion within the ligand binding domain, and showed a ligand-independent, constitutive elevation of tyrosine kinase activity. This EGF-R mutation is detected only in glioma and associated with gene amplification, suggesting a relationship in the molecular mechanism between deletion mutation and initiation of gene amplification in these cases. Secondly I have shown an activation of mouse CD43 gene by amplification and rearrangement in erythroleukemia cell lines. Intracellular domain of CD43 has no kinase domain but a highly conserved structure among mammals, probably interacting with intracellular signal transducers. Recently CD43 has been demonstrated to be specifically associated with a cell-adhesion molecule ICAM-1. Thus, CD43-ICAM-1 system might be a new type of cytokine system which regulate cell-proliferation through cell-cell interaction. In addition, activation of EpoR and v-mpl is also discussed.
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PMID:[Membrane receptors and cell transformation]. 143 60

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

Human glioblastomas are highly malignant intracranial tumors, some of which demonstrate amplification of the epidermal growth factor-receptor (EGF-R) gene. Overexpression of this gene is seen in the majority of primary tumors; however, the role of the EGF-R gene in glial tumorigenesis is unknown. The authors explored the relationship between EGF-R gene expression and glioblastoma cell growth in vitro and in vivo and found that this level of EGF-R gene expression did not correlate with tumor cell growth either in soft agar or in the nude mouse. This suggests that the EGF-R gene is not involved in effecting direct growth stimulation in glial oncogenesis. Tumorigenesis involves differentiation arrest; therefore, the expression of several proto-oncogenes in neuroectodermal tumors was investigated to evaluate the potential involvement of the EGF-R gene in glial differentiation. A nonoverlapping expression of the N-myc and EGF-R genes was found in neuronal-derived and glial-derived tumors, respectively. This suggests that the EGF-R gene may be involved in differentiation or its arrest in glia.
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PMID:Proto-oncogene abnormalities and their relationship to tumorigenicity in some human glioblastomas. 273 45

The gene encoding the receptor for epidermal growth factor was amplified two- to fivefold in the human glioblastoma cell line SF268. The amplified gene gave rise to abundant quantities of receptor that bound EGF with a high affinity (Kd, 0.35 nM). The binding of ligand failed to elicit cellular DNA synthesis, however, and the receptor was enzymatically inactive. We presume that the amplified receptor gene carries a mutation(s) that affects several aspects of the receptor's function. Characterization of the mutation(s) may illuminate how structure dictates function in the receptor protein.
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PMID:Amplified gene for the epidermal growth factor receptor in a human glioblastoma cell line encodes an enzymatically inactive protein. 326 68

Type beta transforming growth factor (B-TGF) is a potent growth inhibitor to many human tumor cell lines. Very little is known about the mechanism for this growth inhibitory action of B-TGF. We here report the effect of B-TGF on proliferation and epidermal growth factor receptor (R-EGF) expression in a human glioblastoma cell line named T-MG1. B-TGF inhibit the soft agar growth of T-MG1 cells. Maximum inhibition was 70%, achieved with 0.5 units B-TGF. B-TGF had no effect on monolayer growth of T-MG1 cells. T-MG1 cells contained abundant R-EGF, which could be divided into two subpopulations, one high affinity and one low affinity population of R-EGF. Treatment with B-TGF caused an initial decrease (0-6 h) in EGF-binding, followed by an increase in EGF-binding which reached maximum after 24 h exposure to B-TGF. Since addition of EGF to agar cultures gave no additional increase in inhibition by B-TGF and EGF alone had no inhibitory effect, we believe that binding of EGF to its receptor is not part of the pathway mediating the inhibitory effect of B-TGF. All neoplastic cells have lost some measure of growth control and the cellular elements involved are growth factors, growth factor receptors and oncogenes. T-MG1 cells contain abundant R-EGF and this may partly explain their malignant nature (malignant nature is here defined as ability to proliferate in agarose). Type alpha transforming growth factors, which in some cancer cells act as uncontrolled autocrine growth factors, were not found in protein extracts from T-MG1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of type beta transforming growth factor on proliferation and epidermal growth factor receptor expression in a human glioblastoma cell line. 326 19

In the human glioblastoma cell line, T-MG1, plasminogen activator activity (PA-activity) was demonstrated by using the chromogenic substrate S-2251. Using monoclonal antibodies against human urokinase type PA (u-PA) and human tissue type PA (t-PA), only u-PA activity was found in T-MG1 cell extracts. The u-PA activity in T-MG1 cells was suppressed in a dose-dependent manner by B-TGF and EGF after 24 hours of exposure to these growth factors. Twenty units of B-TGF caused a decrease in PA-activity of 80%, while 10 ng/ml EGF gave a decrease in PA-activity of 60%. The suppressive effects of B-TGF and EGF were observed after 2 hours and 4 hours of incubation, respectively and sustained for at least 24 hours. The effects of B-TGF and EGF were not antienzymatic, but rather mediated through regulatory mechanisms. In view of the capacity of invasive growth of gliomas and the potential role of PA in invasive growth, the suppression of PA-activity in gliomas by B-TGF and EGF may be of importance.
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PMID:Type beta transforming growth factor and epidermal growth factor suppress the plasminogen activator activity in a human glioblastoma cell line. 326 20

The epidermal growth factor receptor (EGFR) gene is amplified in over 40% of primary human glioblastomas and overexpressed in the majority. The authors' investigations demonstrate that the function of the EGFR in glioblastomas is distinct from that in other human cancers because it does not appear to mediate the primary growth-promoting effect of EGF. Findings show that the level of EGFR expression does not directly predict the growth response to EGF, with growth stimulated in some cells but inhibited in others when cells were cultured in plastic dishes. On the other hand, when human glioblastoma cells were placed in soft agar cultures, the cell line expressing the highest levels of the EGFR demonstrated considerable colony formation in response to EGF treatment. In addition, cell lines with the highest EGFR levels were also more resistant to the growth-suppressive effects of retinoic acid when maintained in soft agar. These observations suggest that even though the overexpression of the EGFR did not confer a distinct growth advantage to glioma cells cultured on flat culture dishes, the ability of these cells to maintain anchorage-independent growth in soft agar especially in response to EGF and retinoic acid is facilitated. Because anchorage-independent growth is the best in vitro correlate to tumorigenicity, amplification and overexpression of the EGFR in human glioblastoma cells may be in part responsible for the tumorigenic potential of these cells.
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PMID:The role of the epidermal growth factor receptor in human gliomas: I. The control of cell growth. 771 11

The most common type of alteration of the epidermal growth factor receptor gene (EGFR) in human glioblastomas results in the synthesis of an aberrant mRNA lacking 801 bases that encode amino acids 6-273 of the receptor's extracellular domain. To study the effects of this mutation on receptor function, we have developed chinese hamster ovary cell transfectants which express the mutant EGF receptor. Comparison of wild-type and mutant receptor properties in this cell host indicates that the truncated receptor does not bind EGF or TGF-alpha and, consequently, DNA synthesis is not stimulated in cultures of mutant transfectants by either grown factor. However, levels of DNA synthesis determined for mutant transfectants in serum-free media are several-fold higher than those determined for corresponding cultures of wild-type transfectants. Western blot analysis with anti-phosphotyrosine antibody indicates that the mutant receptor is constitutively phosphorylated in CHO cells, and the same analysis applied to lysates of glioblastoma biopsies reveals the altered receptor is readily detectable as a phosphotyrosine protein in tumors for which there is evidence of corresponding EGFR gene and transcript alterations. In total, these results indicate that the aberrant EGF receptor synthesized in glioblastomas, and which lacks a portion of the extracellular domain necessary for ligand binding, is an activated tyrosine kinase.
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PMID:Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. 803 13

The development and neoplastic progression of human astrocytic tumors appears to result through an accumulation of genetic alterations occurring in a relatively defined order. One such alteration is amplification of the epidermal growth factor receptor (EGFR) gene. This episomal amplification occurs in 40-50% of glioblastomas, which also normally express endogenous receptors. Moreover, a significant fraction of amplified genes are rearranged to specifically eliminate a DNA fragment containing exons 2-7 of the gene, resulting in an in-frame deletion of 801 bp of the coding sequence of the extracellular domain. Here we used retroviral transfer of such a mutant receptor (de 2-7 EGFR) into glioblastoma cells expressing normal endogenous receptors to test whether the mutant receptor was able to augment their growth and malignancy. Western blotting analysis showed that these cells expressed endogenous EGFR of 170 kDa as well as the exogenous de 2-7 EGFR of 140-155 kDa. Although holo-EGFRs were phosphorylated on tyrosine residues only after exposure of the cells to ligand, de 2-7 EGFRs were constitutively phosphorylated. In tissue culture neither addition of EGF nor expression of the mutant EGFR affected the rate of cell growth. However, when cells expressing mutant EGFR were implanted into nude mice subcutaneously or intracerebrally, tumorigenic capacity was greatly enhanced. These results suggest that a tumor-specific alteration of the EGFR plays a significant role in tumor progression perhaps by influencing interactions of tumor cells with their microenvironment in ways not easily assayed in vitro.
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PMID:A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. 805 51

Human malignant gliomas are frequently associated with loss of gonosomes and chromosomes 13, 17, and 22. Their progression from anaplastic glioma to glioblastoma is marked by additional loss of chromosome 10. In addition, structural and numerical aberrations of chromosome 7 are frequently found. We report on the karyotypes of a series of 20 human gliomas of which 11 were analysed as established cell lines; 9 cases were investigated in early culture, 5 of which later also became established lines. In addition to the frequently reported overrepresentation of chromosome 7, four cell lines with polysomy for chromosome 22 were seen. A high incidence of structural chromosomal aberrations was present in early cultures as well as in cell lines after various in vitro passages. We found that the general characteristics of karyotypic aberrations found in early cultures or direct preparations of dispersed tumour material were reflected in the pattern of aberrations present in cell lines at much later time points. Thus it appears as if no systematic changes can be attributed to long-term cultures. Suspicious losses of chromosomes 14, 18, and 19 or gain of chromosome 22 indicate that individual cases may have originated due to other mechanisms than the ones already hypothesized, i.e., different suppressor genes or amplification of genes other than the EGF-R-gene. None of the established cell lines had a genomic rearrangement of c-erbB 1, c-erbB 2 or of the p 53 gene.
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PMID:Karyotype analyses of 20 human glioma cell lines. 815 17


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