RRC ID 11862
Author Sugihara T, Murano H, Nakamura M, Ichinohe K, Tanaka K.
Title Activation of interferon-stimulated genes by gamma-ray irradiation independently of the ataxia telangiectasia mutated-p53 pathway.
Journal Mol Cancer Res
Abstract The ataxia telangiectasia mutated (ATM)-p53 pathway is a well-known main signal transduction pathway for cellular responses, which is activated by γ-ray irradiation. Microarray analysis showed changes in the expressions of IFN-stimulated genes (ISG) in γ-ray-irradiated Balb/cA/Atm-deficient mouse embryonic fibroblasts (MEF) (ATM-KO), indicating that another pathway for cellular responses besides the ATM-p53 pathway was activated by γ-ray irradiation. The basal expression levels of Irf7 and Stat1 in ATM-KO and p53-deficient MEFs (p53-KO) were higher than those in Atm-wild-type MEFs (ATM-WT) and p53-wild-type MEFs (p53-WT), respectively. Irradiation stimulated the expressions of Irf7 and Stat1 in ATM-KO, p53-KO, ATM-WT, and p53-WT, indicating that upregulation of Irf7 and Stat1 expressions by irradiation did not depend on the ATM-p53 pathway. When conditioned medium (CM) obtained from irradiated ATM-WT or ATM-KO was added to nonirradiated MEFs, the expressions of Irf7 and Stat1 increased. We predicted that gene activation in nonirradiated MEFs was caused by IFN-α/β. Unexpectedly, significant amount of IFN-α/β could not be detected in the CM from irradiated ATM-WT or ATM-KO. Meanwhile, increased expression of Ccl5 (RANTES) protein was detected in the CM from irradiated MEFs. These results indicate that ISGs were activated by γ-ray irradiation independently of the ATM-p53 pathway and gene activation was caused by radiation-induced soluble factors.
Volume 9(4)
Pages 476-84
Published 2011-4-1
DOI 10.1158/1541-7786.MCR-10-0358
PII 1541-7786.MCR-10-0358
PMID 21357441
MeSH Animals Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Chemokine CCL5 / genetics Culture Media, Conditioned / metabolism Culture Media, Conditioned / pharmacology DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Fibroblasts / radiation effects Gamma Rays Gene Expression Regulation / radiation effects Gene Regulatory Networks / genetics Gene Regulatory Networks / radiation effects Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factors / genetics* Interferon Type I / metabolism* Mice Oligonucleotide Array Sequence Analysis Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism* STAT1 Transcription Factor / genetics Signal Transduction / genetics Transcriptional Activation / radiation effects* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 4.63
Times Cited 10
Mice RBRC00107