Published in:
01-06-2012 | Topic Paper
Effect of the heat shock protein HSP27 on androgen receptor expression and function in prostate cancer cells
Authors:
Matthias B. Stope, Tina Schubert, Doreen Staar, Cindy Rönnau, Andreas Streitbörger, Nils Kroeger, Constanze Kubisch, Uwe Zimmermann, Reinhard Walther, Martin Burchardt
Published in:
World Journal of Urology
|
Issue 3/2012
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Abstract
Purpose
Heat shock proteins (HSP) are involved in processes of folding, activation, trafficking and transcriptional activity of most steroid receptors including the androgen receptor (AR). Accumulating evidence links rising heat shock protein 27 (HSP27) levels with the development of castration-resistant prostate cancer. In order to study the functional relationship between HSP27 and the AR, we modulated the expression of the small heat shock protein HSP27 in human prostate cancer (PC) cell lines.
Methods
HSP27 protein concentrations in LNCaP and PC-3 cells were modulated by over-expression or silencing of HSP27. The effects of HSP27 on AR protein and mRNA levels were monitored by Western blotting and quantitative RT-PCR.
Results
Treatment for the AR-positive LNCaP with HSP27-specific siRNA resulted in a down-regulation of AR levels. This down-regulation of protein was paralleled by a decrease in AR mRNA. Most interestingly, over-expression of HSP27 in PC-3 cells led to a significant increase in AR mRNA although the cells were unable to produce functional AR protein.
Conclusion
The observation that HSP27 is involved in the regulation of AR mRNA by a yet unknown mechanism highlights the complexity of HSP27-AR signaling network.