ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE3174 | GEO | 2006/01/15
SECONDARY ACCESSION(S): PRJNA92717
REPOSITORIES: GEO
Similar Datasets
Project description:Investigation of ATM-dependent and dose-dependent, or -independent, responses were examined in human lymphoblast cells 6 hr following exposure to either 1 or 5 Gy ionizing radiation. Human lymphoblast cells from "apparently healthy" individuals and individuals with Ataxia telangiectasia were exposed to 1 Gy or 5 Gy ionizing radiation. Gene expression responses 6 hr following IR were examined. Untreated samples were hybridized together with their matched treated samples.
2010-07-01 | E-GEOD-3174 | biostudies-arrayexpress
Project description:Humans are exposed to ionizing radiation (IR) from background radiation, medical treatments, occupational and accidental exposures. IR causes profound changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines. 12 human primary fibroblast cell lines and 12 primary lymphoblast cell line samples were used for two doses (0 and 10 Gy) and two time points (0 and 4hr). Additional doses ( 1 Gy, 2 Gy, 5 Gy, and 20 Gy) and time points ( 1hr, 2hr, 8hr, 24hr and 48hr) were assessed in four lymphoblast cell lines and four primary fibroblasts.
2011-05-02 | E-GEOD-26841 | biostudies-arrayexpress
Project description:Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by neuronal degeneration, telangiectasias, acute cancer predisposition, and hypersensitivity to ionizing radiation (IR). The gene defective in AT, ATM (for AT-mutated), encodes a protein, pATM that has been found to have IR-inducible kinase activity. Cells from individuals with AT exhibit severely attenuated cell cycle checkpoints in response to gamma radiation exposure. pATM has been hypothesized to act as part of a complex that senses DNA damage, in particular, DNA double strand breaks. We are studying the pATM-dependent gene expression responses to a dose of 1.5 Gy radiation in lymphoblastoid cell lines from multiple individuals with either wild type or mutated ATM. The gene expression analyses were performed on Agilent Human 1A Oligo chips containing approximately 16,000 60mer probes. We identified a set of genes whose gene expression changes are ATM-dependent following exposure to 1.5 Gy IR. This set of genes was tested by real time quantitative PCR analysis.
2013-12-02 | GSE19287 | GEO
Project description:Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by neuronal degeneration, telangiectasias, acute cancer predisposition, and hypersensitivity to ionizing radiation (IR). The gene defective in AT, ATM (for AT-mutated), encodes a protein, pATM that has been found to have IR-inducible kinase activity. Cells from individuals with AT exhibit severely attenuated cell cycle checkpoints in response to gamma radiation exposure. pATM has been hypothesized to act as part of a complex that senses DNA damage, in particular, DNA double strand breaks. We are studying the pATM-dependent gene expression responses to a dose of 1.5 Gy radiation in lymphoblastoid cell lines from multiple individuals with either wild type or mutated ATM. The gene expression analyses were performed on Agilent Human 1A Oligo chips containing approximately 16,000 60mer probes. We identified a set of genes whose gene expression changes are ATM-dependent following exposure to 1.5 Gy IR. This set of genes was tested by real time quantitative PCR analysis. The study consists of one dose group - 1.5 Gray gamma radiation. Samples were collected 6 hr following irradiation (treated) or mock irradiation (controls) for each culture. Each culture has a treated sample and a control sample. There are cultures from 6 wild-type ATM individuals and cultures from 6 individuals that are ATM-deficient, for a total of 12 cultures. Hybridizations compared RNA extracted from each individual culture's treated sample against its corresponding control sample, and were performed as dye-flip duplicates (1 replicate in each direction). Hybridizations were performed on the Human 1A Oligo Chips using low input, direct labeling at Paradigm Genetics Laboratory. Microarray scanning was performed with the Agilent G2565AA Scanner. Paradigm Standard Operating Procedures were followed for quality analysis, sample labeling, microarray hybridization and washing, scanning, image analysis and initial data analysis.
2013-12-02 | E-GEOD-19287 | biostudies-arrayexpress
Project description:The DNA damage response network modulates a wide array of signaling pathways, including DNA repair, cell cycle checkpoints, apoptotic pathways and numerous stress signals. The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia (A-T), is a master regulator of this network when the inducing DNA lesions are double strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combines gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation (IR) in murine lymphoid tissue. Cluster analysis revealed six major expression patterns in the data. Prominent among them was a gene cluster that contained dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of the transcription factors NF-kB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and anti-apoptotic signals were simultaneously induced, with the pro-apoptotic pathway mediated by p53, and the pro-survival pathway by NF-kB. These findings further elucidate the molecular network induced by IR and have implications for cancer management as they suggest that a combined treatment that restores the p53-mediated apoptotic arm while blocking the NF-kB-mediated pro-survival arm could be most successful in increasing the radiosensitivity of lymphoid tumors.
2007-12-04 | E-GEOD-2118 | biostudies-arrayexpress
Project description:Time series for gene expression changes following 3 Gy and 10 Gy of ionizing radiation exposure. Keywords: time-course
2003-10-08 | GSE701 | GEO
Project description:Human embryonic stem cells (hESCs) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs. In this study, we use Agilent microarrays to analyze the global gene expression changes in H9 hESCs after low (0.4 Gy), medium (2 Gy), and high (4 Gy) dose irradiation.
2010-06-16 | GSE20951 | GEO
Project description:Time series for gene expression changes following 3 Gy and 10 Gy of ionizing radiation exposure.
2007-09-21 | E-GEOD-701 | biostudies-arrayexpress
Project description:DNA repair is an essential cellular process required to maintain genomic stability. Every cell is subjected to thousands of DNA lesions daily under normal changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines. 12 human primary fibroblast cell lines and 12 primary lymphoblast cell line samples were used for two doses (0 and 10 Gy) and two time points (0 and 4hr). Additional doses ( 1 Gy, 2 Gy, 5 Gy, and 20 Gy) and time points ( 1hr, 2hr, 8hr, 24hr and 48hr) were assessed in four primary lymphoblast cell lines and four primary fibroblasts.
2012-10-26 | E-GEOD-41840 | biostudies-arrayexpress
Project description:Human embryonic stem cells (hESCs) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs. In this study, we use Agilent microarrays to analyze the global gene expression changes in H9 hESCs after low (0.4 Gy), medium (2 Gy), and high (4 Gy) dose irradiation. Undifferentiated H9 hESCs were cultured on Matrigel in feeder-free conditions, and exposed to ionizing radiation at the indicated dosage (or control) from a Cesium-137 irradiator. Total RNA was isolated 24 hours after irradiation in the same feeder-free culture conditions. Experiment was repeated three times for each group, yielding a total of 12 distinct samples.
2010-07-08 | E-GEOD-20951 | biostudies-arrayexpress