In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 µg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.
Oncotarget. 2017 Jan 06 [Epub ahead of print]
Dieuwertje E G Kok, Lambertus A L M Kiemeney, Gerald W Verhaegh, Jack A Schalken, Emile N J T van Lin, J P Michiel Sedelaar, J Alfred Witjes, Christina A Hulsbergen-van de Kaa, Pieter Van't Veer, Ellen Kampman, Lydia A Afman
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands., Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Strahlentherapie Bonn Rhein Sieg, Wesel, Germany., Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.