| RRC ID |
43152
|
| 著者 |
Futami K, Kumagai E, Makino H, Goto H, Takagi M, Shimamoto A, Furuichi Y.
|
| タイトル |
Induction of mitotic cell death in cancer cells by small interference RNA suppressing the expression of RecQL1 helicase.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
RecQL1 DNA helicase of the human RecQ helicase family participates in DNA repair and recombination pathways during cell-cycle replication. When we examined the effect of RecQL1 suppression on cell growth, we found that RecQL1 silencing by small interference RNA efficiently prevented proliferation of a wide range of cancer cells by inducing mitotic catastrophe and mitotic cell death. In contrast, such mitotic cell death was not seen in the growing normal fibroblasts used as controls, even if RecQL1 expression was fully downregulated. Our results support the hypothesis that endogenous DNA damage that occurs during DNA replication and remains unrepaired in cancer cells due to RecQL1 silencing induces cancer cell-specific mitotic catastrophe through a less-strict checkpoint in cancer cells than in normal cells. We speculate that normal cells are exempt from such mitotic cell death, despite slow growth, because cell-cycle progression is controlled strictly by a strong checkpoint system that detects DNA damage and arrests progression of the cell cycle until DNA damage is repaired completely. These results suggest that RecQL1 helicase is an excellent molecular target for cancer chemotherapy.
|
| 巻・号 |
99(1)
|
| ページ |
71-80
|
| 公開日 |
2008-1-1
|
| DOI |
10.1111/j.1349-7006.2007.00647.x
|
| PII |
CAS647
|
| PMID |
17953710
|
| MeSH |
Cell Death / genetics
Cell Growth Processes / physiology
Cell Line, Tumor
DNA Damage
DNA Repair
Down-Regulation
Gene Silencing
HCT116 Cells
HeLa Cells
Humans
Microscopy, Fluorescence
Mitosis / genetics
Neoplasms / enzymology*
Neoplasms / genetics*
Neoplasms / pathology
RNA, Small Interfering / genetics*
RecQ Helicases / antagonists & inhibitors
RecQ Helicases / biosynthesis
RecQ Helicases / genetics*
|
| IF |
4.966
|
| 引用数 |
40
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
T24(RCB0431) |
