ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression

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*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

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 hor-moneablation 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.

Original languageEnglish (US)
Pages (from-to)1031-1040
Number of pages10
JournalNeoplasia
Volume12
Issue number12
DOIs
Publication statusPublished - Jan 1 2010

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Rickman, D. S., Chen, Y. B., Banerjee, S., Pan, Y., Yu, J., Vuong, T., ... Demichelis, F. (2010). ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression. Neoplasia, 12(12), 1031-1040. https://doi.org/10.1593/neo.10866