A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate
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Dieuwertje E.G. Kok1, Lambertus A.L.M. Kiemeney2,3, Gerald W. Verhaegh3, Jack A. Schalken3, Emile N.J.T. van Lin4, J.P. Michiel Sedelaar3, J. Alfred Witjes3, Christina A. Hulsbergen - van de Kaa5, Pieter van ’t Veer1, Ellen Kampman1,2, Lydia A. Afman1
1Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
2Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands
3Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands
4Strahlentherapie Bonn Rhein Sieg, Wesel, Germany
5Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
Lydia A. Afman, email: [email protected]
Keywords: selenium, prostatic neoplasms, gene expression, microarray, EMT
Received: February 06, 2016 Accepted: December 16, 2016 Published: January 06, 2017
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.
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