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Lookup NU author(s): Dr Ian Logan, Dr Urszula McClurg, Dr Dominic Jones, Daniel O'Neill, Dr Fadhel Shaheen, Professor John LunecORCiD, Dr Luke GaughanORCiD, Professor Craig Robson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Inhibition of androgen receptor (AR) signalling represents the conventional medical management of prostate cancer. Ultimately this treatment fails because tumors develop an incurable, castrate resistant phenotype, resulting in an unmet need for new treatments in prostate cancer. The AR remains a viable therapeutic target in castrate resistant disease, such that novel ways of downregulating AR activities are attractive as potential treatments. Here we describe a mechanism by which the AR can be downregulated by the MDM2 antagonist Nutlin-3, resulting in loss of pro-survival c-FLIP gene expression and apoptosis. We additionally show that loss of c-FLIP sensitises prostate cancer cells to Nutlin-3. Finally, we demonstrate that the unrelated MDM2 antagonist Mi-63 also impinges upon AR signalling, supporting the concept of future treatment of prostate cancer with MDM2 antagonists.
Author(s): Logan IR, McClurg UL, Jones DL, O'Neill DJ, Shaheen FS, Lunec J, Gaughan L, Robson CN
Publication type: Article
Publication status: Published
Journal: Oncotarget
Year: 2016
Volume: 7
Issue: 46
Pages: 74724-74733
Online publication date: 09/10/2016
Acceptance date: 26/09/2016
Date deposited: 18/04/2017
ISSN (electronic): 1949-2553
Publisher: Impact Journal LLC
URL: http://dx.doi.org/10.18632/oncotarget.12542
DOI: 10.18632/oncotarget.12542
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