| Inhibition of Aurora-B function increases formation of multinucleated cells in p53 gene deficient cells and enhances anti-tumor effect of temozolomide in human glioma cells. | |
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MedLine Citation:
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PMID: 17570035 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell division is an elemental process, and mainly consists of chromosome segregation and subsequent cytokinesis. Some errors in this process have the possibility of leading to carcinogenesis. Aurora-B is known as a chromosomal passenger protein that regulates cell division. In our previous studies of giant cell glioblastoma, we reported that multinucleated giant cells resulted from aberrations in cytokinesis with intact nuclear division occurring in the early mitotic phase, probably due to Aurora-B dysfunction. In this study, as we determined p53 gene mutation occurring in multinucleated giant cell glioblastoma, we investigated the role of Aurora-B in formation of multinucleated cells in human neoplasm cells with various p53 statuses as well as cytotoxity of glioma cells to temozolomide (TMZ), a common oral alkylating agent used in the treatment of gliomas. The inhibition of Aurora-B function by small-interfering (si)RNA led to an increase in the number of multinucleated cells and the ratios of G2/M phase in p53-mutant and p53-null cells, but not in p53-wild cells or the cells transduced adenovirally with wild-p53. The combination of TMZ and Aurora-B-siRNA remarkably inhibited the cell viability of TMZ-resistant glioma cells. Accordingly, our results suggested that Aurora-B dysfunction increases in the appearance of multinucleated cells in p53 gene deficient cells, and TMZ treatment in combination with the inhibition of Aurora-B function may become a potential therapy against p53 gene deficient and chemotherapeutic-resistant human gliomas. |
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Authors:
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Takaya Tsuno; Atsushi Natsume; Shun Katsumata; Masaaki Mizuno; Mitsugu Fujita; Hirokatsu Osawa; Norimoto Nakahara; Toshihiko Wakabayashi; Yu-ichiro Satoh; Masaki Inagaki; Jun Yoshida |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-02-14 |
Journal Detail:
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Title: Journal of neuro-oncology Volume: 83 ISSN: 0167-594X ISO Abbreviation: J. Neurooncol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-15 Completed Date: 2007-08-09 Revised Date: 2011-07-11 |
Medline Journal Info:
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Nlm Unique ID: 8309335 Medline TA: J Neurooncol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 249-58 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Alkylating
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therapeutic use* Blotting, Western Brain Neoplasms / drug therapy*, genetics, pathology Cell Cycle / drug effects Cell Survival / drug effects Dacarbazine / analogs & derivatives*, therapeutic use Flow Cytometry Giant Cells / pathology* Glioma / drug therapy*, genetics, pathology Humans Mutation / genetics Protein-Serine-Threonine Kinases / antagonists & inhibitors* RNA, Small Interfering / pharmacology Tumor Cells, Cultured / drug effects Tumor Suppressor Protein p53 / genetics*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 0/RNA, Small Interfering; 0/Tumor Suppressor Protein p53; 4342-03-4/Dacarbazine; 85622-93-1/temozolomide; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/aurora kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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