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.
Titolo: | ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression. |
Autori: | D. S., Rickman; Y., Chen; S., Banerjee; Y., Pan; J., Yu; T., Vuong; S., Perner; C. J., Lafargue; K. D., Mertz; S. R., Setlur; K., Sircar; A. M., Chinnaiyan; T. A., Bismar; M. A., Rubin; Demichelis, Francesca |
Autori Unitn: | |
Titolo del periodico: | NEOPLASIA |
Anno di pubblicazione: | 2010 |
Codice identificativo Scopus: | 2-s2.0-78649890593 |
Codice identificativo Pubmed: | 21170267 |
Codice identificativo ISI: | WOS:000285209400008 |
Handle: | http://hdl.handle.net/11572/88956 |
Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |