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ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression

Authors :
David S. Rickman
Ying-bei Chen
Samprit Banerjee
Yihang Pan
Jindan Yu
Terry Vuong
Sven Perner
Christopher J. Lafargue
Kirsten D. Mertz
Sunita R. Setlur
Kanishka Sircar
Arul M. Chinnaiyan
Tarek A. Bismar
Mark A. Rubin
Francesca Demichelis
Source :
Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 12, Pp 1031-1040 (2010)
Publication Year :
2010
Publisher :
Elsevier, 2010.

Abstract

To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC), we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3) emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hormone ablation therapy. Conventional chromatin immunoprecipitation (ChIP)-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq) revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC) and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.

Details

Language :
English
ISSN :
14765586 and 15228002
Volume :
12
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Neoplasia: An International Journal for Oncology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.876ca2a9970d494a845acaf9db49ed2d
Document Type :
article
Full Text :
https://doi.org/10.1593/neo.10866