title: Immediate and transient phosphorylation of the heat shock protein 27 initiates chemoresistance in prostate cancer cells.
abstract: Drug resistance minimizes the effects of prostate cancer (PC) chemotherapy with docetaxel and is generally considered to be associated with the expression of heat shock protein (HSP) 27 including various cytoprotective pathways. In the present study, we investigated the effects of HSP27 phosphorylation on PC cell growth underlying docetaxel treatment. Cell counting revealed significantly reduced cell growth during docetaxel treatment as a result of both activation of mitogen-activated protein kinase p38 (MAPK p38) and protein kinase D1 (PKD1), and, most importantly, the overexpression of the phosphorylation-mimicking mutant HSP27-3D. Further analysis revealed a docetaxel-dependent induction of HSP27 accompanied by an initial phosphorylation and rapid dephosphorylation of the protein. Based on the data, we can conclude that phosphorylation of HSP27 protein is a crucial mechanism in the initiation of chemoresistance in PC. Moreover, the results indicate a key impact of HSP27 on viability and proliferation of PC cells underlying anticancer therapy. The protective function depends on the initial phosphorylation status of HSP27 and represents a putative co-therapeutic target to prevent chemoresistance during docetaxel therapy.
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Preuss
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Streitbörger
authors.affiliation: Institute of Pharmacy, Ernst-Moritz-Arndt-University of Greifswald, Greifswald, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Ritter
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Zimmermann
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Burchardt
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D055551:HSP27 Heat-Shock Proteins; D043823:Taxoids; D000077143:Docetaxel