A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate

// Dieuwertje E.G. Kok 1 , Lambertus A.L.M. Kiemeney 2, 3 , Gerald W. Verhaegh 3 , Jack A. Schalken 3 , Emile N.J.T. van Lin 4 , J.P. Michiel Sedelaar 3 , J. Alfred Witjes 3 , Christina A. Hulsbergen - van de Kaa 5 , Pieter van ’t Veer 1 , Ellen Kampman 1, 2 , Lydia A. Afman 1 1 Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands 2 Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands 3 Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands 4 Strahlentherapie Bonn Rhein Sieg, Wesel, Germany 5 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands Correspondence to: Lydia A. Afman, email: lydia.afman@wur.nl Keywords: selenium, prostatic neoplasms, gene expression, microarray, EMT Received: February 06, 2016      Accepted: December 16, 2016      Published: January 06, 2017 ABSTRACT 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.