論文 - 詳細
RRC ID | 11862 |
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著者 | Sugihara T, Murano H, Nakamura M, Ichinohe K, Tanaka K. |
タイトル | Activation of interferon-stimulated genes by gamma-ray irradiation independently of the ataxia telangiectasia mutated-p53 pathway. |
ジャーナル | 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. |
巻・号 | 9(4) |
ページ | 476-84 |
公開日 | 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 |
引用数 | 10 |
WOS 分野 | ONCOLOGY CELL BIOLOGY |
リソース情報 | |
実験動物マウス | RBRC00107 |