title: Over-expression of IkappaB-kinase-epsilon (IKKepsilon/IKKi) induces secretion of inflammatory cytokines in prostate cancer cell lines.
abstract: 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.
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal/Institut du cancer de Montréal, Québec, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Péant
authors.forename: Jean-Simon
authors.initials: JS
authors.lastname: Diallo
authors.forename: Florent
authors.initials: F
authors.lastname: Dufour
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Page
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delvoye
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D014162:Transfection
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase