Background: Advanced prostate cancer (PCa) remains a one of the leading causes of cancer related death and is often due to the progression from a hormone sensitive (HS) to a castrate resistant (CR) state for which therapeutic alternatives remain palliative. Molecular events involved in the progression to CR-PCa remain largely unknown. A previous study reported significantly higher levels of Iκ-B kinase-epsilon (IKKε) expression in CR compared to androgen-responsive cell lines. In the present study, we evaluate IKKε expression in human prostate tissue.
Methods: In order to evaluate the modulation of IKKε expression in PCa tissue IKKε immunostaining was performed on paraffin-embedded prostate tissue microarrays containing cores from normal tissues (n = 47), non-malignant tissues adjacent to the tumor (n = 53), prostatic intraepithelial neoplasia (PIN) (n = 28), HS (n = 62), and CR tumors (n = 31).
Results: We found a low cytoplasmic expression of IKKε in non-malignant tissue. HS tumors showed a significant increase in cytoplasmic IKKε expression compared to non-malignant tissues. CR tissues presented the highest cytoplasmic IKKε expression levels. We also report, for the first time, the presence of a nuclear localization of IKKε in prostate epithelial cells, in particular we observed an increase of IKKε nuclear localization in HS malignant tissues. Finally, we found a strong link between an increase of IKKε cytoplasmic expression in PCa and metastatic progression.
Conclusion: This study strongly suggests the role of IKKε as a PCa oncogene that may be involved in the emergence of a CR state.
Copyright © 2011 Wiley-Liss, Inc.