Title | ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Rickman DS, Chen Y-B, Banerjee S, Pan Y, Yu J, Vuong T, Perner S, Lafargue CJ, Mertz KD, Setlur SR, Sircar K, Chinnaiyan AM, Bismar TA, Rubin MA, Demichelis F |
Journal | Neoplasia |
Volume | 12 |
Issue | 12 |
Pagination | 1031-40 |
Date Published | 2010 Dec |
ISSN | 1476-5586 |
Keywords | Chromatin Immunoprecipitation, Disease Progression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Invasiveness, Neoplasms, Hormone-Dependent, Peptides, Polymerase Chain Reaction, Prostatic Neoplasms, Receptors, Androgen, Sequence Analysis, DNA, Signal Transduction, Trans-Activators, Transcription Factors |
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. |
Alternate Journal | Neoplasia |
PubMed ID | 21170267 |
PubMed Central ID | PMC3003138 |
Grant List | K99 CA129565 / CA / NCI NIH HHS / United States R00 CA129565 / CA / NCI NIH HHS / United States R00 CA129565-03 / CA / NCI NIH HHS / United States R01 CA125612-01 / CA / NCI NIH HHS / United States |