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

Dieuwertje E.G Kok,J.P Michiel Sedelaar,Emile N.J.T Van Lin,J Alfred Witjes,Lambertus A.L.M Kiemeney,Jack A Schalken,Lydia A Afman,Gerald W Verhaegh,Ellen Kampman,Pieter Van ’T Veer,Christina A Hulsbergen - Van De Kaa

doi:10.18632/oncotarget.14551

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.

Highlights

Based on early observational and intervention studies, it has been suggested that an adequate status or intake of selenium may protect against prostate cancer [1,2,3,4]
Selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to epithelial-to-mesenchymal transition (EMT)
Our study demonstrated that a 5-week intervention with selenium was associated with changes in expression of genes implicated in EMT in non-malignant prostate tissue

Summary

Introduction

Based on early observational and intervention studies, it has been suggested that an adequate status or intake of selenium may protect against prostate cancer [1,2,3,4]. The Nutritional Prevention of Cancer (NPC) trial showed that 200 μg selenized yeast per day reduced the incidence of prostate cancer, and advanced prostate cancer in particular [2]. Did not consistently confirm a protective effect of selenium for prostate cancer [5,6,7,8]. E Cancer Prevention (SELECT) trial demonstrated that supplements with 200 μg L-selenomethionine did not decrease the incidence of prostate cancer among men in the general population [6, 9]. In men at high risk for prostate cancer, 200-400 μg of selenized yeast per day was not effective for prostate cancer prevention [8]

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