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Research Paper
Calcium/Calmodulin-Dependent Kinase II Plays an Important Role in Prostate Cancer Cell Survival
Oskar Rokhlin, Agshin F. Taghiyev, Ulrich K. Bayer, David Bumcrot, Victor E Kotelianski, Rebecca A. Glover and Michael B. Cohen
volume 6 | issue 5
May 2007Pages: 732 - 742
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It has recently been shown that the androgen receptor (AR) is the main factor that required for prostate cancer cells survival. We show that knocking down AR expression by siRNA induces PI3K-independent activation of Akt, which was mediated by calcium/calmodulin-dependent kinase II (CaMKII). We further show, for the first time, that prostate cancer cells express β, γ, and δ CaMKII genes, and the expression of these genes is under the control of AR activity: active AR in the presence of androgens inhibits CaMKII gene expression whereas inhibition of AR activity results in elevated level of kinase activity and in enhanced expression of CaMKII-β and –γ genes. Overexpression of CaMKII genes results in resistance to apoptosis induced by KN-93, a CaMKII inhibitor, or wortmanninn, a PI3K/Akt inhibitor, in combination with doxorubicin, thapsigargin and TRAIL. Moreover, overexpression of CaMKII increases secretion of prostate specific antigen and promotes cell growth of LNCaP in steroid-free condition. Our data show that there is cross-talk between AR- and CaMKII-mediated pathways. The results of this study suggest that CaMKII is an important player in prostate cancer cells ability to escape apoptosis under androgen ablation and facilitate the progression of prostate cancer cells to an androgen-independent state.
Authors
Oskar Rokhlin
University of Iowa, Iowa City, Iowa
Agshin F. Taghiyev
University of Iowa, Iowa City, Iowa
Ulrich K. Bayer
University of Colorado Health Science Center, Denver, CO
David Bumcrot
Alnylam Pharmaceutical, Cambridge, MA
Victor E Kotelianski
Alnylam Pharmaceutical, Cambridge, MA
Rebecca A. Glover
University of Iowa, Iowa City, Iowa
Michael B. Cohen
University of Iowa; Iowa City IA, USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.