title: IκB-Kinase-ε (IKKε/IKKi/IκBKε) expression and localization in prostate cancer tissues.
abstract: 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.
  
  
  CONCLUSIONS
  This study strongly suggests the role of IKKε as a PCa oncogene that may be involved in the emergence of a CR state.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM)/Institut du Cancer de Montréal, Québec, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Péant
authors.forename: Valérie
authors.initials: V
authors.lastname: Forest
authors.forename: Vincent
authors.initials: V
authors.lastname: Trudeau
authors.forename: Mathieu
authors.initials: M
authors.lastname: Latour
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D051550:I-kappa B Kinase