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.
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 CRtumors (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.
Authors: D Bauer; N Redmon; E Mazzio; E Taka; J S Reuben; A Day; S Sadrud-Din; H Flores-Rozas; K F A Soliman; S Darling-Reed Journal: Cytokine Date: 2015-06-20 Impact factor: 3.861
Authors: Moritz Möller; Julia Wasel; Julia Schmetzer; Ulrike Weiß; Markus Meissner; Susanne Schiffmann; Andreas Weigert; Christine V Möser; Ellen Niederberger Journal: Int J Mol Sci Date: 2020-07-02 Impact factor: 5.923
Authors: Alex Bainbridge; Scott Walker; Joseph Smith; Kathryn Patterson; Aparna Dutt; Yi Min Ng; Huw D Thomas; Laura Wilson; Benjamin McCullough; Dominic Jones; Arussa Maan; Peter Banks; Stuart R McCracken; Luke Gaughan; Craig N Robson; Kelly Coffey Journal: Nucleic Acids Res Date: 2020-06-04 Impact factor: 16.971
Authors: Benjamin Péant; Sophie Gilbert; Cécile Le Page; Alexis Poisson; Emilie L'Ecuyer; Zied Boudhraa; Marc Nicolas Bienz; Nathalie Delvoye; Fred Saad; Anne-Marie Mes-Masson Journal: Oncotarget Date: 2017-02-28
Authors: Ruoyan Xu; William Jones; Ewa Wilcz-Villega; Ana Sh Costa; Vinothini Rajeeve; Robert B Bentham; Kevin Bryson; Ai Nagano; Busra Yaman; Sheila Olendo Barasa; Yewei Wang; Claude Chelala; Pedro Cutillas; Gyorgy Szabadkai; Christian Frezza; Katiuscia Bianchi Journal: EMBO Rep Date: 2020-08-11 Impact factor: 8.807