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

Oncotarget. 2017 Feb 7;8(6):10565-10579. 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.

Keywords: EMT; gene expression; microarray; prostatic neoplasms; selenium.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Dietary Supplements*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects*
  • Gene Regulatory Networks
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Oligonucleotide Array Sequence Analysis
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Selenium / administration & dosage*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Time Factors
  • Transcriptome

Substances

  • Selenium