| Induction of mitotic cell death in cancer cells by small interference RNA suppressing the expression of RecQL1 helicase. | |
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MedLine Citation:
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PMID: 17953710 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kazunobu Futami; Emi Kumagai; Hiroshi Makino; Hideyuki Goto; Motoki Takagi; Akira Shimamoto; Yasuhiro Furuichi |
Publication Detail:
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Type: Journal Article Date: 2007-10-22 |
Journal Detail:
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Title: Cancer science Volume: 99 ISSN: 1349-7006 ISO Abbreviation: Cancer Sci. Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2007-12-18 Completed Date: 2008-02-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: England |
Other Details:
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Languages: eng Pagination: 71-80 Citation Subset: IM |
Affiliation:
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GeneCare Research Institute, 19-2 Kajiwara, Kamakura, Kanagawa 247-0063, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Death
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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*, genetics*, pathology RNA, Small Interfering / genetics* RecQ Helicases / antagonists & inhibitors, biosynthesis, genetics* |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; EC 3.6.1.-/RecQ Helicases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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