School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia
Research Article
Implications of Androgen Receptor Hyperstimulation by the FKBP51 L119P Mutation: No Evidence for Early Emergence of L119P in Prostate Cancer
Author(s): Bryan K Ward*, Carmel Cluning, Ajanthy Arulpragasam, Jacqueline M Bentel, David C Chandler, Ronald J Cohen, Gunnar Fischer, Michael R Epis, Peter J Leedman, Wayne D Tilley, Australian Prostate Cancer BioResource, Lisa Butler, Jessica Savage, Renea Taylor, Melissa Papargiris, Jenna Vangramberg, Trina Yeadon, Allison Eckert, Jyotsna Batra, Pamela Saunders, Anne-Maree Haynes, Lisa Horvarth, Gail Risbridger and Thomas Ratajczak
Objective: The immunophilin cochaperones, FKBP51 and FKBP52, have a modulating effect on steroid hormone receptors including the androgen receptor (AR). The differential effects seen by these immunophilins can be attributed to amino acid differences in the proline-rich loop; the proline at position 119 conferring AR potentiation capacity on FKBP52 and the leucine at this position in FKBP51 diminishing potentiation. FKBP51 can nevertheless potentiate AR activity in prostate cancer cells leading to accelerated growth. In addition, FKBP51 is regulated by AR, providing a feed-forward mechanism for FKBP51-mediated AR potentiation. These observations suggest that development of the FKBP51-L119P mutation in rostate cancer could lead to increased potentiation of AR and a more aggressive cancer phenotype. We tested this theory by examining the prevalence of FKBP51-L119P in a c.. View More»
