You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2012469 IDENTIFICATION OF THE NOVEL PROSTATE CANCER BIOMARKER TDRD1 AS A DIRECT TARGET GENE OF ERG IN PRIMARY PROSTATE CANCER Joost Boormans, Hanneke Korsten, and Jan Trapman Joost BoormansJoost Boormans Rotterdam, Netherlands More articles by this author , Hanneke KorstenHanneke Korsten Rotterdam, Netherlands More articles by this author , and Jan TrapmanJan Trapman Rotterdam, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.538AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genomic rearrangements involving fusion of the androgen-regulated gene TMPRSS2 to the oncogene ERG, are frequently present in prostate cancer (PCa). The significance of fusion genes involving ETS family members in the development and progression of PCa is still largely unknown. In the present study, we used genome-wide expression analysis and quantitative reverse transcription-PCR (Q-RT-PCR) to identify genes that were coexpressed with ERG overexpression in different stages of PCa. METHODS RNA was isolated form clinical PCa samples and expression profiles were determined using the GeneChip Human Exon 1.0 ST array according to the manufacterer's instructions. Expression data were obtained form primary PCa (n=48), PCa lymph node metastases (n=12), recurrent PCa (n=9), normal adjacent prostatic tissue (n=17), PCa cell lines (n=6), and PCa xenografts (n=11). By significance of microarrays (SAM), genes coexpressed with ERG were identified. For validation purposes, an additional cohort of 31 primary PCa was analyzed by Q-RT-PCR as was the expression data of 128 primary PCa samples from a different institution that were available through a web-based portal (http://cbio.mskcc.org/prostate-portal). Furthermore, functional studies were carried out in the PCa cell line VCaP to study direct ERG regulated genes. RESULTS Analysis of gene expression profiles of the primary PCa cohort (cohort A, n=48) showed Tudor domain containing 1 (TDRD1) to be the strongest correlated gene with ERG overexpression. This observation was confirmed by Q-RT-PCR for cohort A and for an independent cohort of primary PCa (n=31). Analysis of expression array data of a cohort of primary PCa from a different institution (n=128) showed a large overlap in genes that were positively correlated with ERG overexpression, including TDRD1. In VCaP, downregulation of ERG by infection with a lentivirus expressing a specific shRNA lead to a substantial lower expression level of the TDRD1 protein. Furthermore, it was shown that ERG regulates TDRD1 expression as inactivation of ERG by siRNA resulted in a decreased activity of the TDRD1 promoter. In this promoter, a functional ERG binding site was identified. In late-stage prostate cancer, TDRD1 was also coexpressed with ERG overexpression, although a proportion of ERG-negative late-stage samples harbored TDRD1 expression as well. CONCLUSIONS Our findings indicate that TDRD1 is a direct target gene of ERG and in primary PCa the expression of TDRD1 is strongly associated with ERG overexpression. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e192 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joost Boormans Rotterdam, Netherlands More articles by this author Hanneke Korsten Rotterdam, Netherlands More articles by this author Jan Trapman Rotterdam, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...