Document Detail

A mutation in beta-tubulin and a sustained dependence on androgen receptor signalling in a newly established docetaxel-resistant prostate cancer cell line.
MedLine Citation:
PMID:  19947927     Owner:  NLM     Status:  MEDLINE    
The mechanisms of docetaxel resistance in PC (prostate cancer) are unclear because of the lack of suitable experimental models, and no effective treatment exists for docetaxel-resistant PC. We established a docetaxel-resistant cell line, LNDCr, from an androgen-refractory PC cell line, LNCaP-hr, by intermittent exposure to docetaxel in vitro. The LNDCr cells harboured an F270I mutation in class I beta-tubulin, and demonstrated impaired tubulin polymerization by docetaxel. AR signalling was sustained in LNDCr cells, and AR knockdown suppressed the growth of LNDCr cells. These results suggest that an acquired mutation in beta-tubulin is associated with docetaxel resistance in PC and that a novel AR-targeted therapy is effective for docetaxel-resistant PC.
Takahito Hara; Kazutaka Ushio; Mayumi Nishiwaki; Jin Kouno; Hideo Araki; Yukiko Hikichi; Masahiko Hattori; Yumi Imai; Masuo Yamaoka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-25
Journal Detail:
Title:  Cell biology international     Volume:  34     ISSN:  1095-8355     ISO Abbreviation:  Cell Biol. Int.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-08-04     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  177-84     Citation Subset:  IM    
Pharmacology Research Laboratories, Takeda Pharmaceutical Company Limited, Tsukuba, Japan.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Drug Resistance, Neoplasm
Prostatic Neoplasms / metabolism*
RNA Interference
RNA, Small Interfering
Receptors, Androgen / genetics,  metabolism*
Signal Transduction*
Taxoids / pharmacology*
Tubulin / genetics*,  metabolism
Reg. No./Substance:
0/AR protein, human; 0/Antineoplastic Agents; 0/RNA, Small Interfering; 0/Receptors, Androgen; 0/Taxoids; 0/Tubulin; 15H5577CQD/docetaxel

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