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.
This is an open access article distributed under the
Creative Commons Attribution License which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
Export to BibTeX
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.