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

Gene amplification, which is generally considered to occur late in tumor development, is a common feature of high grade glioma. Up until now, there have been no reports on amplification in astrocytoma grade I. In this study, we report cloning and sequencing of a cDNA termed glioma-amplified sequence (GAS41) which was identified recently in a glioblastoma cell line by microdissection-mediated cDNA capture. This technique is tailored to isolate amplified genes from human tumors. An increased copy number of GAS41 was found in glioblastoma multiforme and astrocytoma III, and at a high frequency in astrocytoma grades I and II. Sequence comparison indicates a high homology between the GAS41 protein, the yeast and human AF-9 and the human ENL proteins. Both AF-9 and ENL belong to a new class of transcription factors, indicating that GAS41 might also represent a transcription factor. With GAS41 being the first gene found with increased copy number in low grade glioma, this study provides the first evidence that gene amplification can occur in early tumor development.
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PMID:Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I. 930 58

The glioma amplified sequence 41 (GAS41) was previously isolated by microdissection mediated cDNA capture from the glioblastoma multiforme cell line TX3868 and shown to be frequently amplified in human gliomas. We determined the complete cDNA sequence of the GAS41 gene, demonstrated that the GAS41 protein is evolutionarily conserved, specifically at the N-terminus, and identified the yeast transcription factor tf2f domain within the GAS41 sequence. A human multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the highest expression in human brain. After generating polyclonal antibodies we found GAS41 protein expression in the nucleus of the TX3868 cell line by Western blot analysis and immunofluorescence microscopy. The nuclear localization was confirmed for several human tumors including gliomas of different grades of malignancy. In neuroblastoma however, GAS41 was found in the nucleoli but not in the nucleoplasm. Yeast two-hybrid screening of the TX3868 cell line identified the nuclear mitotic apparatus protein (NuMA), the KIAA1009 protein, and prefoldin subunit 1 (PFDN1) as potential interacting partners of GAS41. We generated a polyclonal antibody against the KIAA1009 protein and we demonstrated that the KIAA1009 protein is a nuclear protein, which appears to be co-localized with the GAS41 protein and NuMA.
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PMID:Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor. 1152 Nov 96

The glioma-amplified sequence (GAS) 41 protein has been proposed to be a transcription factor. To investigate its functional role in vivo, we attempted to knock out the GAS41 gene by targeted disruption in the chicken pre-lymphoid cell line DT40. Heterozygous GAS41+/- cell lines generated by the first round of homologous recombination express approximately half the normal level of GAS41 mRNA. However, a homozygous GAS41-/- cell line with both GAS41 alleles disrupted was not obtained following the second round of transfection, indicating that the GAS41 gene is essential for cell viability. Indeed, homozygous GAS41-/- cell lines with two disrupted GAS41 alleles can be generated following substitution of the endogenous gene by stable integration of GAS41 cDNA controlled by a tetracycline-regulated CMV promoter. Inactivation of this promoter by tetracycline withdrawal results in rapid depletion of GAS41, causing a significant decrease in RNA synthesis and subsequently cell death. Thus, our results indicate that GAS41 is required for RNA transcription.
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PMID:Targeted disruption of the GAS41 gene encoding a putative transcription factor indicates that GAS41 is essential for cell viability. 1190 Nov 57

Dysregulation of the human transforming acidic coiled-coil (TACC) proteins is thought to be important in the evolution of breast cancer and multiple myeloma. However, the exact role of these proteins in the oncogenic process is currently unknown. Using the full-length TACC1 protein as bait to screen a human mammary epithelial cDNA library, we have identified two genes that are also amplified and overexpressed in tumours derived from different cellular origins. TACC1 interacts with the C-terminus of both the microtubule-associated colonic and hepatic tumour overexpressed (ch-TOG) protein, and the oncogenic transcription factor glioma amplified sequence 41/NuMA binding protein 1 (GAS41/NuBI1; where NuMA stands for nuclear mitotic apparatus protein 1). This suggests that the TACC proteins can form multiple complexes, dysregulation of which may be an important step during tumorigenesis.
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PMID:Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells. 1190 63

To further understand the biological significance of amplifications for glioma development and recurrencies, we characterized amplicon frequency and size in low-grade glioma and amplicon stability in vivo in recurring glioblastoma. We developed a 12q13-21 amplicon-specific genomic microarray and a bioinformatics amplification prediction tool to analyze amplicon frequency, size, and maintenance in 40 glioma samples including 16 glioblastoma, 10 anaplastic astrocytoma, 7 astrocytoma WHO grade 2, and 7 pilocytic astrocytoma. Whereas previous studies reported two amplified subregions, we found a more complex situation with many amplified subregions. Analyzing 40 glioma, we found that all analyzed glioblastoma and the majority of pilocytic astrocytoma, grade 2 astrocytoma, and anaplastic astrocytoma showed at least one amplified subregion, indicating a much higher amplification frequency than previously suggested. Amplifications in low-grade glioma were smaller in size and displayed clearly different distribution patterns than amplifications in glioblastoma. One glioblastoma and its recurrencies revealed an amplified subregion of 5 Mb that was stable for 6 years. Expression analysis of the amplified region revealed 10 overexpressed genes (i.e., KUB3, CTDSP2, CDK4, OS-9, DCTN2, RAB3IP, FRS2, GAS41, MDM2, and RAP1B) that were consistently overexpressed in all cases that carried this amplification. Our data indicate that amplifications on 12q13-21 (a) are more frequent than previously thought and present in low-grade tumors and (b) are maintained as extended regions over long periods of time.
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PMID:A different view on DNA amplifications indicates frequent, highly complex, and stable amplicons on 12q13-21 in glioma. 1840 36

The 5'-flanking region of the chicken glioma-amplified sequence (GAS) 41 gene is close to the 3' end of the lysozyme gene and contains no typical TATA box, but several GC boxes. In this study, we have localized the GAS 41 promoter to this narrow region. Electrophoretic mobility shift assays and chromatin immunoprecipitation analyses revealed that Sp1 and Sp3 bind to this promoter. Mapping by a technique of indirect end labeling demonstrated that the Sp1-binding sites contained in this region exactly co-map with two previously identified DNase I hypersensitive (HS) sites, which suggests the important role of Sp1 binding in maintaining an open chromatin structure of the GAS41 promoter. We further found that Sp1 and Sp3 strongly activate CAT expression controlled by the putative GAS41 promoter in Drosophila Schneider S2 cells and that deletion of the Sp1 sites resulted in a loss of promoter activity in chicken HD11 cells. The results indicate that transcription factors of the Sp family play an important role in the transcriptional regulation of the chicken GAS41 gene.
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PMID:Sp1 and Sp3 regulate transcription of the chicken GAS41 gene. 2015 53

YEATS domain containing 4 (YEATS4) is usually amplified and functions as an oncogene in human glioma. However, the biological role of YEATS4 in colorectal cancer (CRC) has not yet been discussed. In this study, we investigated the expression level of YEATS4 in 85 pairs of CRC and paracancerous tissues, and knocked down YEATS4 via a lentivirus system in RKO CRC cell line. Although YEATS4 was upregulated in CRC tissues, YEATS4 expression showed no association with any clinical features and overall survival. Inhibition of YEATS4 significantly suppressed cell proliferation and colony formation. Flow cytometry revealed that cell cycle was arrested in the G0/G1 phase and the number of apoptotic cells were significantly increased when YEATS4 expression was inhibited. In conclusion, our findings provide first evidence that YEATS4 may be an important regulator of cell proliferation and apoptosis in CRC cells.
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PMID:Knockdown of YEATS4 inhibits colorectal cancer cell proliferation and induces apoptosis. 2604

Glioma amplified sequence 41(GAS41) is a potent transcription factor that play a crucial role in cell proliferation and survival. In glioblastoma, the expression of GAS41 at both transcriptional and post transcriptional level needs to be tightly maintained in response to cellular signals. Micro RNAs (miRNA) are small non coding RNA that act as important regulators for modulating the expression of various target genes. Studies have shown that several miRNAs play role in the post-transcriptional regulation of GAS41. Here we identified GAS41 as a novel target for endogenous miR-203 and demonstrate an inverse correlation of miR-203 expression with GAS41 in glioma cell lines (HNGC2 and U87). Over expression of miR-203 negatively regulates GAS41 expression in U87 and HNGC2 cell lines. Moreover, miR-203 restrained miR-10b action by suppressing GAS41. GAS41 is essential for repressing p53 in tumor suppressor pathway during cell proliferation. Enforced expression of GAS41 produced contradictory effect on miR-203 but was able to enhance p53 tumor suppressor pathway associated protein. It was also found that miR-203 maintains the stability of p53 as knock down of p53 expression using siRNA resulted in down regulation of pri-miR and mature miR-203 expression. Conversely reconstitution of miR-203 expression induced apoptosis and inhibited migratory property of glioma cells. Taken together, we show that miR-203 is a key negative regulator of GAS41 and acts as tumor suppressor microRNA in glioma.
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PMID:Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells. 2746 2