ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression
| Autor: | Francesca Demichelis, David S. Rickman, Mark A. Rubin, Kanishka Sircar, Arul M. Chinnaiyan, Tarek A. Bismar, Jindan Yu, Sunita R. Setlur, Sven Perner, Ying bei Chen, Kirsten D. Mertz, Terry Vuong, Samprit Banerjee, Christopher J. LaFargue, Yihang Pan |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Regulation of gene expression
0303 health sciences Cancer Research genetic structures Trefoil factor 3 Cancer Biology medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Molecular biology lcsh:RC254-282 3. Good health Androgen receptor 03 medical and health sciences Prostate cancer 0302 clinical medicine 030220 oncology & carcinogenesis medicine sense organs Chromatin immunoprecipitation Erg 030304 developmental biology Transcriptional Regulator ERG |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 12, Pp 1031-1040 (2010) |
| ISSN: | 1522-8002 1476-5586 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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