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Int. J. Mol. Sci. 2012, 13(9), 11530-11542; doi:10.3390/ijms130911530
Article

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

1,2,†,* , 3,†
,
1
,
1
,
2
,
1
 and
2
1 Department of Urology, Ulm University, Ulm 89075, Germany 2 Department of Physiology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin 14195, Germany 3 Institute of General Zoology and Endocrinology, Ulm University, Ulm 89069, Germany These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 August 2012 / Revised: 5 September 2012 / Accepted: 6 September 2012 / Published: 14 September 2012
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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Abstract

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.
Keywords: sorafenib; truncated androgen receptor variants; castration resistant prostate cancer sorafenib; truncated androgen receptor variants; castration resistant prostate cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Zengerling, F.; Streicher, W.; Schrader, A.J.; Schrader, M.; Nitzsche, B.; Cronauer, M.V.; Höpfner, M. Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells. Int. J. Mol. Sci. 2012, 13, 11530-11542.

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