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

International Journal of Molecular Sciences

Friedemann Zengerling³  Wolfgang Streicher²  Andres J. Schrader³  Mark Schrader³  Bianca Nitzsche¹  Marcus V. Cronauer³ 

[1] Department of Physiology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin 14195, Germany; E-Mails:;Institute of General Zoology and Endocrinology, Ulm University, Ulm 89069, Germany; E-Mail:;Department of Urology, Ulm University, Ulm 89075, Germany; E-Mails:

关键词: sorafenib;    truncated androgen receptor variants;    castration resistant prostate cancer;   

DOI  :  10.3390/ijms130911530

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.