Kok Dieuwertje E G, Kiemeney Lambertus A L M, Verhaegh Gerald W, Schalken Jack A, van Lin Emile N J T, Sedelaar J P Michiel, Witjes J Alfred, Hulsbergen-van de Kaa Christina A, van 't Veer Pieter, Kampman Ellen, Afman Lydia A
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Oncotarget. 2017 Feb 7;8(6):10565-10579. doi: 10.18632/oncotarget.14551.
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.
与观察性研究和化学预防试验结果的不一致情况类似,硒影响前列腺癌风险的机制尚未阐明。我们开展了一项随机、安慰剂对照试验,以研究短期补充硒对非恶性前列腺组织中基因表达的影响。23名男性在5周内每天接受300微克以硒化酵母形式存在的硒(n = 12)或安慰剂(n = 11)。对15名参与者(n = 8接受硒,n = 7接受安慰剂)干预前后从移行带采集的前列腺活检组织进行了分析。通路分析显示,补充硒与细胞迁移、侵袭、重塑和免疫反应相关基因的表达下调有关。具体而言,在补充硒干预后,成熟的上皮标志物如E-钙黏蛋白和上皮细胞黏附分子EPCAM的表达上调,而间充质标志物波形蛋白和纤连蛋白的表达下调。这意味着硒对上皮-间质转化(EMT)具有抑制作用。此外,硒与伤口愈合和炎症相关基因的表达下调有关;而这两个过程均与EMT相关。总之,我们的探索性数据表明,硒影响前列腺移行带中与EMT相关的基因表达。