Reference - Detail
| RRC ID | 42809 |
|---|---|
| Author | Noguchi M, Yu D, Hirayama R, Ninomiya Y, Sekine E, Kubota N, Ando K, Okayasu R. |
| Title | Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. |
| Journal | Biochem Biophys Res Commun |
| Abstract |
In order to investigate the mechanism of radio-sensitization by an Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), we studied repair of DNA double strand breaks (DSBs) in irradiated human cells pre-treated with 17-AAG. DSBs are thought to be the critical target for radiation-induced cell death. Two human tumor cell lines DU145 and SQ-5 which showed clear radio-sensitization by 17-AAG revealed a significant inhibition of DSB repair, while normal human cells which did not show radio-sensitization by the drug indicated no change in the DSB repair kinetics with 17-AAG. We further demonstrated that BRCA2 was a novel client protein for Hsp90, and 17-AAG caused the degradation of BRCA2 and in turn altered the behavior of Rad51, a critical protein for homologous recombination (HR) pathway of DSB repair. Our data demonstrate for the first time that 17-AAG inhibits the HR repair process and could provide a new therapeutic strategy to selectively result in higher tumor cell killing. |
| Volume | 351(3) |
| Pages | 658-63 |
| Published | 2006-12-22 |
| DOI | 10.1016/j.bbrc.2006.10.094 |
| PII | S0006-291X(06)02331-X |
| PMID | 17083915 |
| MeSH | Apoptosis / drug effects* Apoptosis / radiation effects* Benzoquinones / administration & dosage* Cell Line, Tumor DNA Repair / drug effects* Dose-Response Relationship, Drug Dose-Response Relationship, Radiation HSP90 Heat-Shock Proteins / antagonists & inhibitors* Humans Lactams, Macrocyclic / administration & dosage* Male Prostatic Neoplasms / genetics* Prostatic Neoplasms / pathology Radiation Dosage Radiation Tolerance / drug effects Recombination, Genetic / drug effects* Recombination, Genetic / genetics Recombination, Genetic / radiation effects |
| IF | 2.985 |
| Times Cited | 90 |
| WOS Category | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | SQ-5(RCB0110) |