%0 Journal Article
%T Functional Epigenetic Analysis of Prostate Carcinoma: A Role for Seryl-tRNA Synthetase?
%A Odiljon Ikromov
%A Imad Alkamal
%A Ahmed Magheli
%A Nadine Ratert
%A Mauricio Sendeski
%A Kurt Miller
%A Hans Krause
%A Carsten Kempkensteffen
%J Journal of Biomarkers
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/362164
%X Transcriptional silencing, as a result of aberrant promoter hypermethylation, is a common mechanism through which genes in cancer cells become inactive. Functional epigenetic screens using demethylating agents to reexpress transcriptional silenced genes may identify such inactivated genes for needing further evaluation. We aimed to identify genes so far not known to be inactivated by promoter hypermethylation in prostate cancer. DU-145 and LNCaP cells were treated with the DNMT inhibitor zebularine. Expression changes of total RNA from treated and untreated cells were compared using an RNA expression microarray. Genes upregulated more than 2-fold were evaluated by RT-qPCR in 50 cases of paired normal and tumor tissues of prostate cancer patients. SARS was found to be downregulated in prostate cancer in 42/50 cases (84%). In addition, GADD45A and SPRY4 showed a remarkable diminished expression (88% and 74%, resp.). The gold standard for promoter hypermethylation-inactivated genes in prostate cancer (GSTP1) was repressed in 90% of our patient samples. ROC analyses reported statistically significant AUC curves in SARS, GADD45A, and GSTP1 and positive Spearman correlations were found between these genes. SARS was discovered to be a novel gene that is repressed in prostate cancer and could therefore be recommended for its involvement in prostate carcinogenesis. 1. Introduction Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth leading cause of cancer death among men worldwide, with 1111,689 new cases and 307,471 (6.6%) deaths projected to occur in 2012 [1]. In 2013, cancers of the prostate, lung and bronchus, and colorectum will account for about 50% of all newly diagnosed cancers in the United States; prostate cancer alone will account for 28% (238,500) of incident cases [2]. In Germany, prostate cancer is already the third most cause of cancer death with more than 68,000 newly diagnosed cases (25.2%) and a mortality rate of approximately 12,500 men (10.7%) in 2012 [1]. Despite extensive scientific efforts and technological progress, the molecular mechanisms of development and progression in particular to lethal PCa are still elusive and need further investigation. Genetic and epigenetic alterations in prostate tumorigenesis, as in all other cancers, accumulate within a multistep transformation process on the cellular level [3, 4]. Aberrant DNA promoter CpG islands hypermethylation of genes is a well-characterized mechanism for transcriptional silencing of tumour suppressor genes in various cancers [5]. Epigenetic silencing
%U http://www.hindawi.com/journals/jbm/2014/362164/