Over-expression of IkappaB-kinase-epsilon (IKKepsilon/IKKi) induces secretion of inflammatory cytokines in prostate cancer cell lines.


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 Ikappa-B kinase-epsilon (IKKepsilon/IKKi)-deficiency results in the reduction of lipopolysaccharide-mediated expression of IL-6. RESULTS In this study, we report that over-expression of IKKepsilon 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 IKKepsilon knock-down in these cells correlates with a strong decrease in IL-6 secretion. Furthermore, we demonstrate that IKKepsilon over-expression does not induce the activation of the IKKepsilon classical targets NF-kappaB and IRF-3, two transcription factors involved in the regulation of several cytokines. Finally, we observe that high IKKepsilon expression results in its nuclear translocation, a phenomena that is TBK1-independent. CONCLUSIONS This study identifies IKKepsilon 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.

DOI: 10.1002/pros.20912
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@article{Pant2009OverexpressionOI, title={Over-expression of IkappaB-kinase-epsilon (IKKepsilon/IKKi) induces secretion of inflammatory cytokines in prostate cancer cell lines.}, author={Benjamin P{\'e}ant and J Diallo and Florent Dufour and C{\'e}cile Le Page and Nathalie Delvoye and Fred Saad and Anne-Marie Mes-Masson}, journal={The Prostate}, year={2009}, volume={69 7}, pages={706-18} }