| RRC ID |
42809
|
| 著者 |
Noguchi M, Yu D, Hirayama R, Ninomiya Y, Sekine E, Kubota N, Ando K, Okayasu R.
|
| タイトル |
Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin.
|
| ジャーナル |
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.
|
| 巻・号 |
351(3)
|
| ページ |
658-63
|
| 公開日 |
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
|
| 引用数 |
90
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
SQ-5(RCB0110) |
