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Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR). A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the...

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Autores principales: Zengerling, Friedemann, Streicher, Wolfgang, Schrader, Andres J., Schrader, Mark, Nitzsche, Bianca, Cronauer, Marcus V., Höpfner, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472761/
https://www.ncbi.nlm.nih.gov/pubmed/23109869
http://dx.doi.org/10.3390/ijms130911530
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author Zengerling, Friedemann
Streicher, Wolfgang
Schrader, Andres J.
Schrader, Mark
Nitzsche, Bianca
Cronauer, Marcus V.
Höpfner, Michael
author_facet Zengerling, Friedemann
Streicher, Wolfgang
Schrader, Andres J.
Schrader, Mark
Nitzsche, Bianca
Cronauer, Marcus V.
Höpfner, Michael
author_sort Zengerling, Friedemann
collection PubMed
description Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR). A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the expression of constitutively active, C-terminally truncated AR lacking the AR-ligand binding domain (LBD). Due to the absence of a LBD, these receptors, termed ARΔLBD, are unable to respond to any form of anti-hormonal therapies. In this study we demonstrate that the multikinase inhibitor sorafenib inhibits AR as well as ARΔLBD-signalling in CRPCa cells. This inhibition was paralleled by proteasomal degradation of the AR- and ARΔLBD-molecules. In line with these observations, maximal antiproliferative effects of sorafenib were achieved in AR and ARΔLBD-positive PCa cells. The present findings warrant further investigations on sorafenib as an option for the treatment of advanced AR-positive PCa.
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spelling pubmed-34727612012-10-29 Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells Zengerling, Friedemann Streicher, Wolfgang Schrader, Andres J. Schrader, Mark Nitzsche, Bianca Cronauer, Marcus V. Höpfner, Michael Int J Mol Sci Article Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR). A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the expression of constitutively active, C-terminally truncated AR lacking the AR-ligand binding domain (LBD). Due to the absence of a LBD, these receptors, termed ARΔLBD, are unable to respond to any form of anti-hormonal therapies. In this study we demonstrate that the multikinase inhibitor sorafenib inhibits AR as well as ARΔLBD-signalling in CRPCa cells. This inhibition was paralleled by proteasomal degradation of the AR- and ARΔLBD-molecules. In line with these observations, maximal antiproliferative effects of sorafenib were achieved in AR and ARΔLBD-positive PCa cells. The present findings warrant further investigations on sorafenib as an option for the treatment of advanced AR-positive PCa. Molecular Diversity Preservation International (MDPI) 2012-09-14 /pmc/articles/PMC3472761/ /pubmed/23109869 http://dx.doi.org/10.3390/ijms130911530 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zengerling, Friedemann
Streicher, Wolfgang
Schrader, Andres J.
Schrader, Mark
Nitzsche, Bianca
Cronauer, Marcus V.
Höpfner, Michael
Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
title Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
title_full Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
title_fullStr Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
title_full_unstemmed Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
title_short Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
title_sort effects of sorafenib on c-terminally truncated androgen receptor variants in human prostate cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472761/
https://www.ncbi.nlm.nih.gov/pubmed/23109869
http://dx.doi.org/10.3390/ijms130911530
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