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Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells
Department of Urology, Ulm University, Ulm 89075, Germany
Department of Physiology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin 14195, Germany
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; in revised form: 5 September 2012 / Accepted: 6 September 2012 / Published: 14 September 2012
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
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MDPI and ACS Style
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.
Zengerling F, Streicher W, Schrader AJ, Schrader M, Nitzsche B, Cronauer MV, Höpfner M. Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells. International Journal of Molecular Sciences. 2012; 13(9):11530-11542.
Zengerling, Friedemann; Streicher, Wolfgang; Schrader, Andres J.; Schrader, Mark; Nitzsche, Bianca; Cronauer, Marcus V.; Höpfner, Michael. 2012. "Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells." Int. J. Mol. Sci. 13, no. 9: 11530-11542.