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Series GSE2118 Query DataSets for GSE2118
Status Public on Dec 20, 2005
Title IR-response in Atm-/- and control lymph nodes
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Keywords: ordered
 
 
Contributor(s) Rashi-Elkeles S, Elkon R, Weizman N, Linhart C, Amarglio N, Sternberg G, Rechavi G, Barzilai A, Shamir R, Shiloh Y
Citation(s) 16314843
Submission date Jan 01, 2005
Last update date Feb 18, 2018
Contact name Ran Elkon
Organization name Tel Aviv University
Department Human Genetics
Street address Ramat Aviv
City Tel Aviv
ZIP/Postal code 69494
Country Israel
 
Platforms (1)
GPL81 [MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array
Samples (14)
GSM38262 Atm+/+ untreated A
GSM38263 Atm+/+ untreated B
GSM38264 Atm+/+ untreated C
Relations
BioProject PRJNA91779

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Supplementary file Size Download File type/resource
GSE2118_RAW.tar 38.2 Mb (http)(custom) TAR (of CEL)

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