title: A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.
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.
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Dieuwertje E G
authors.initials: DE
authors.lastname: Kok
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands.
authors.forename: Lambertus A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Verhaegh
authors.affiliation: Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
authors.affiliation: Strahlentherapie Bonn Rhein Sieg, Wesel, Germany.
authors.forename: Emile N J T
authors.initials: EN
authors.lastname: van Lin
authors.affiliation: Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands.
authors.forename: J P Michiel
authors.initials: JP
authors.lastname: Sedelaar
authors.affiliation: Department of Urology, Radboud university Medical Center, Nijmegen, The Netherlands.
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Hulsbergen-van de Kaa
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: van 't Veer
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.|Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kampman
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Afman
mesh_terms: D000368:Aged; D019587:Dietary Supplements; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012643:Selenium / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D059467:Transcriptome
chemical_list: D012643:Selenium
keywords: EMT; gene expression; microarray; prostatic neoplasms; selenium