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)

The human platelet-derived growth factor (PDGF) A-chain locus was characterized by restriction endonuclease analysis, and the nucleotide sequence of its exons was determined. Seven exons were identified, spanning approximately 22 kilobase pairs of genomic DNA. Alternative exon usage, identified by cDNA cloning, occurs in a human glioblastoma cell line and may give rise to two types of A-chain precursors with different C termini. The exon-intron arrangement was similar to that of the PDGF B-chain/sis locus and seemed to divide the precursor proteins into functional domains. Southern blot analysis of genomic DNA showed that a single PDGF A-chain gene was present in the human genome.
Mol Cell Biol 1988 Feb
PMID:Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: alternative exon usage predicts two different precursor proteins. 283 27

We have studied the regulation by glucocorticoids and dibutyryl cAMP of the amounts of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and a Mr approximately 54000 plasminogen activator inhibitor accumulated in serum-free conditioned culture fluid by a human fibrosarcoma, a human glioblastoma and a human melanoma cell line (HT-1080, UCT/gl-1 and Bowes). For the quantitation of u-PA and t-PA, we used sandwich-type ELISA with a combination of polyclonal and monoclonal antibodies. For an estimation of variations in the amount of the inhibitor, we used sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by Coomassie blue staining of conditioned culture fluid proteins, the inhibitor protein band being identified by its selective removal by passage of the conditioned culture fluids through a column with monoclonal antibodies against the inhibitor. The modulation of the 3 proteins by the hormonal agents varied greatly between the cell lines. The proteins were independently regulated, in the sense that the hormonal agents did not concomitantly change their levels in the direction expected either to increase or decrease total extracellular plasminogen activator activity. In conditioned culture fluids containing both t-PA and inhibitor, the two were present in the medium as a Mr approximately 120 000 complex. In contrast, no u-PA inhibitor complexes were found in conditioned culture fluid from any of the cell lines; this is likely to be due to the occurrence of u-PA in the culture fluid in the one-chain proenzyme form, which, unlike active u-PA, does not react with the inhibitor. These findings illustrate the complexity of the regulation of extracellular plasminogen activator activity, and imply that the presumed functional diversity of u-PA and t-PA may be related to their independent regulation.
Mol Cell Endocrinol 1986 May
PMID:Hormonal regulation of extracellular plasminogen activators and Mr approximately 54,000 plasminogen activator inhibitor in human neoplastic cell lines, studied with monoclonal antibodies. 301 58

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.
Mol Cell Biol 1988 Oct
PMID:Amplified gene for the epidermal growth factor receptor in a human glioblastoma cell line encodes an enzymatically inactive protein. 326 68

B-cell stimulatory factor 2 (BSF-2) is a lymphokine which induces the final maturation of B cells. BSF-2 acts on a variety of cells other than B cells, and moreover, expression of BSF-2 mRNA is detected in interleukin-1 beta-stimulated glioblastoma and astrocytoma cell lines. Here, we studied the function of BSF-2 on pheochromocytoma PC12 cells, a model system for induction of neuronal differentiation. PC12 cells possess specific receptors for BSF-2. The BSF-2-stimulated PC12 cells expressed the c-fos proto-oncogene transiently, and they began to change morphologically to neurite-extending cells after several days. The number of voltage-dependent Na+ channels was also increased.
Mol Cell Biol 1988 Aug
PMID:Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. 326 80

Results of previous studies have shown that a raf-related transforming DNA sequence is present in NIH 3T3 transformants that are derived from GL-5-JCK human glioblastoma DNA transfection. The transforming DNA was molecularly cloned by using cosmid vector pJB8 to determine its structure and origin. Analyses of selected clones revealed that the transforming DNA consisted of three portions of human DNA sequences, with the 3' half of the c-raf-1 gene as its middle portion. This raf region was about 20 kilobases long and contained exons 8 to 17 and the poly(A) addition site. RNA blot analysis showed that the raf-related transforming DNA was transcribed into 5.3-, 4.8-, and 2.5-kilobase mRNAs; the 2.5-kilobase transcript was thought to be the major transcript. Immunoprecipitation analyses revealed that a 44-kilodalton raf-related protein was specifically expressed in the NIH 3T3 transformants. The raf-related transforming DNA was considered to be activated when its amino-terminal sequence was truncated and the DNA was coupled with a foreign promoter sequence. On hybridization analysis of the original GL-5-JCK glioblastoma DNA, no rearrangement of c-raf-1 was detectable in the tumor DNA. The rearrangement of c-raf-1 may have occurred during transfection or may have been present in a small population of the original tumor cells as a result of tumor progression.
Mol Cell Biol 1987 May
PMID:Molecular cloning and characterization of an activated human c-raf-1 gene. 329 54

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.
Mol Cell Biol 1988 Apr
PMID:Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. 338 99

In addition to its synthesis in the developing placenta, human CG or the isolated alpha- and beta-subunits are synthesized by a wide variety of both trophoblastic and nontrophoblastic tumor cell lines. The beta-subunit confers unique biological activity on the hormone and is encoded by a family of six genes or pseudogenes linked physically with beta LH at one locus on chromosome 19. Previous work has demonstrated that members of the beta CG family are not expressed to the same extent in first-trimester placenta. The factors allowing differential expression of the six nearly identical genes are unknown. It is also undetermined which of the multiple beta CG genes are actively expressed in the tumor cell lines that produce beta-subunit ectopically. One potential mechanism for control of beta CG gene expression is DNA methylation. A unique method of two-dimensional DNA electrophoresis was used to analyze the methylation status of each of the individual beta CG genes in placenta and in tumor cell lines that either do or do not express the protein. The DNA from each source exhibited unique, reproducible methylation patterns over the six beta CG genes. Particularly interesting were the observations that: 1) despite their nearly identical sequences and close chromosomal proximity, the six beta CG genes are distinguished from one another within the same and different cell types by their extent and pattern of methylation; 2) the beta CG locus is significantly hypomethylated in placenta, a state maintained in choriocarcinoma cells (JAr); 3) the beta CG gene cluster is unmethylated at a limited set of sites in DNA from both 2RA (a transformed fibroblast cell line that does not produce beta-subunit) and CBT (a glioblastoma cell line that produces beta-subunit ectopically), suggesting that general demethylation of the domain does not accompany activation of the locus in CBT but rather that site-specific changes may be responsible, at least in part, for inappropriate beta CG expression; and 4) the ratio of beta CG gene 3 transcripts to beta CG gene 5 transcripts is at least 10-fold higher in CBT cells than in JAr cells, suggesting that the reduced methylation in CBT cells of gene 3 compared to gene 5 may be a factor contributing to the activity of these genes.
Mol Endocrinol 1993 Oct
PMID:Differential DNA methylation of the chorionic gonadotropin beta-subunit multigene family. 750 95

The primary transcript of the calcitonin (CT)/calcitonin gene-related peptide (CGRP) is alternatively spliced in a cell-specific fashion to produce CT in thyroid C cells and CGRP in neuronal cells. The key step in this regulatory process is the recognition and inclusion of exon 4 to produce CT mRNA or nonrecognition and exclusion of exon 4 to produce CGRP mRNA. To determine whether inclusion/exclusion of CT exon is regulated independently of its position, we created a series of minigene constructs containing decreasing amounts of CT gene sequence. A human glioblastoma cell line, T98G, was tested and used as a CT exon exclusion cell line, while HeLa cells were used as a CT exon inclusion cell line. CT exon inclusion/exclusion was regulated when either the relative position of exon 4 within the CT gene was changed or when the exon with flanking sequence was inserted into a completely heterologous gene. Our results demonstrate that CT exon functions as a unit in a position-independent fashion in regulating its own inclusion/exclusion. We believe that the heterologous fusion gene containing only exon 4 and part of its flanking intron sequences will be useful for further defining the sequence elements involved in the regulation of CT/CGRP splicing.
Mol Endocrinol 1994 Dec
PMID:The calcitonin exon and its flanking intronic sequences are sufficient for the regulation of human calcitonin/calcitonin gene-related peptide alternative RNA splicing. 753 92

Several transcription regulatory elements that interact with cellular DNA-binding proteins have been identified in the HIV-1 long terminal repeat (LTR). We have identified two sequence motifs in the U3 region of the LTR that are similar to the consensus 9-bp DNA-binding element of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. One of the sequences (promoter-proximal) mapped immediately upstream of the NF-kappa B element, whereas the other (promoter-distal) completely overlapped the upstream stimulatory factor (USF) binding site. In this study, we investigated the role of the enhancer-proximal consensus C/EBP binding sequence in the expression of the HIV-1 LTR. In cotransfection assays we found that although this sequence is a functional C/EBP-responsive element, the regulation of the HIV promoter by C/EBP is very complex. C/EBP isoforms inhibited the phorbol 12-myristate 13-acetate (PMA)-stimulated HIV-1 promoter activity in human glioblastoma U138MG and neuroblastoma SHSY5Y cells, but not in HeLa epithelial cells, and this inhibition required the NF-kappa B element. C/EBP also downregulated the HIV NF-kappa B element-containing SV40 early promoter activity, regardless of the presence of the flanking C/EBP-binding sequences, in the two brain-derived cells. In electrophoretic mobility shift assays with nuclear extracts from HeLa and U138MG cells, purified C/EBP markedly increased the complex formation between endogenous proteins and the NF-kappa B DNA probe without detectable association with the complex. However, with extracts from U138MG cells but not from HeLa cells, a slow migrating complex was observed. Our data suggest that the C/EBP family of transcription factors can downregulate the HIV-1 promoter activity in CNS-derived cells through the NF-kappa B binding elements.
J Mol Neurosci
PMID:NF-kappa B site-mediated negative regulation of the HIV-1 promoter by CCAAT/enhancer binding proteins in brain-derived cells. 757 67

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


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