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Estramustine resistance correlates with tau over‐expression in human prostatic carcinoma cells
Author(s) -
Sangrajrang Suleeporn,
Denoulet Philippe,
Millot Guy,
Tatoud Roger,
Podgorniak MariePierre,
Tew Kenneth D.,
Calvo Fabien,
Fellous Arlette
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980812)77:4<626::aid-ijc24>3.0.co;2-2
Subject(s) - du145 , estramustine , phosphoprotein , tau protein , phosphorylation , microtubule , tyrosine phosphorylation , biology , microtubule polymerization , cancer research , cell culture , tyrosine , tubulin , cancer cell , prostate cancer , microbiology and biotechnology , cancer , medicine , biochemistry , prostate disease , genetics , disease , alzheimer's disease , lncap
Estramustine (EM) is an anti‐microtubule drug used in the treatment of hormone‐refractory advanced prostate cancer. Since microtubules are the targets for EM cytotoxicity, we investigated the effects of EM on the microtubule‐associated protein tau to determine what role it may play in drug resistance. We have compared tau expression in human prostate cancer cells (DU145) and an EM‐resistant derived cell line (E4). Reverse transcriptase polymerase chain reaction has established that tau is expressed in both cell lines but increased 1.9‐fold in E4 compared with DU145 cells. This result was confirmed at the protein level by Western blotting. Tau is a phosphoprotein, most of its reported phosphorylation sites being serine or threonine residues. We have shown, however, that tau is also phosphorylated at tyrosine residues in DU145 cells and that the phosphotyrosine level of tau is significantly increased in E4 cells. Moreover, DU145 cells exposed to short term micromolar drug concentrations enter a phase of microtubule depolymerization, display an increased level of tau phosphorylation and follow a pattern similar to that observed in EM‐resistant E4 cells. EM is therefore able to induce a very rapid change in the post‐translational state of tau. Our results show that the acquisition of EM resistance in E4 cells, which is accompanied by changes at the tubulin level, is also associated with important changes in tau expression and phosphorylation. Int. J. Cancer 77:626–631, 1998. © 1998 Wiley‐Liss, Inc.