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IκB‐Kinase‐ε (IKKε/IKKi/IκBKε) expression and localization in prostate cancer tissues
Author(s) -
Péant Benjamin,
Forest Valérie,
Trudeau Vincent,
Latour Mathieu,
MesMasson AnneMarie,
Saad Fred
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21329
Subject(s) - prostate cancer , tissue microarray , iκb kinase , prostate , cancer research , oncogene , cancer , kinase , pathology , tumor progression , biology , medicine , cell cycle , signal transduction , nf κb , microbiology and biotechnology
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. Prostate 71:1131–1138, 2011. © 2011 Wiley‐Liss, Inc.