Journal
PROSTATE
Volume 69, Issue 7, Pages 706-718Publisher
WILEY-BLACKWELL
DOI: 10.1002/pros.20912
Keywords
prostate cancer; IKK epsilon/IKKi; cytokine secretion; IL-6; IL-8
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Funding
- CHUM urology department
- Prostate Cancer Research Foundation of Canada
- Canderel and Marc Bourgie Foundation
- Universite de Montreal Chair in Prostate Cancer Research
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BACKGROUND. Elevated inflammatory cytokine levels in serum have been associated with advanced stage metastasis-related morbidity in prostate cancer. Several studies have shown that IL-6 and IL-8 can accelerate the growth of human prostate cancer cell lines. Previous studies, in murine embryonic fibroblasts, have shown that I kappa-B kinase-epsilon (IKK epsilon/IKKi)-deficiency results in the reduction of lipopolysaccharide-mediated expression of IL-6. RESULTS. In this study, we report that over-expression of IKK epsilon in hormone-sensitive 22Rv1 and LNCaP prostate cancer cells induces the secretion of several inflammatory cytokines including IL-6 and IL-8. Both of these cytokines are secreted by hormone-refractory PC-3 prostate cancer cells and IKK epsilon knock-down in these cells correlates with a strong decrease in IL-6 secretion. Furthermore, we demonstrate that IKK epsilon over-expression does not induce the activation of the IKK epsilon classical targets NF-kappa B and IRF-3, two transcription factors involved in the regulation of several cytokines. Finally, we observe that high IKK epsilon expression results in its nuclear translocation, a phenomena that is TBK1-independent. CONCLUSIONS. This study identifies IKK epsilon as a potential prostate cancer gene that may favor chronic inflammation and create a tumor-supporting microenvironment that promotes prostate cancer progression, particularly by the induction of IL-6 secretion that may act as a positive growth factor in prostate cancer. Prostate 69: 706-718, 2009. (C) 2009 Wiley-Liss, Inc.
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