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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2010) 34, 177–184 (Printed in Great Britain)
A mutation in β-tubulin and a sustained dependence on androgen receptor signalling in a newly established docetaxel-resistant prostate cancer cell line
Takahito Hara*1, Kazutaka Ushio*, Mayumi Nishiwaki*, Jin Kouno*, Hideo Araki*, Yukiko Hikichi*, Masahiko Hattori*, Yumi Imai† and Masuo Yamaoka*
*Pharmacology Research Laboratories, Takeda Pharmaceutical Company Limited, Tsukuba, Japan, and †Discovery Research Center, Takeda Pharmaceutical Company Limited, Osaka, Japan

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 β-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 β-tubulin is associated with docetaxel resistance in PC and that a novel AR-targeted therapy is effective for docetaxel-resistant PC.

Key words: androgen receptor, docetaxel, drug resistance, prostate cancer, tubulin

Abbreviations: ABC, ATP-binding cassette, AR, androgen receptor, DCC-FBS, dextran charcoal-stripped fetal bovine serum, FBS, fetal bovine serum, PC, prostate cancer, PSA, prostate-specific antigen, siRNA, small interfering RNA

1To whom correspondence should be addressed (email

Received 15 May 2009/13 October 2009; accepted 22 October 2009

Published as Cell Biology International Immediate Publication 22 October 2009, doi:10.1042/CBI20090030

© 2010 The Author(s) Journal compilation. © 2010 Portland Press Ltd

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)