ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression
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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2010-12-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558610800211 |
| _version_ | 1828952393707945984 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | David S. Rickman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T06:52:24Z |
| format | Article |
| id | doaj.art-876ca2a9970d494a845acaf9db49ed2d |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-14T06:52:24Z |
| publishDate | 2010-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-876ca2a9970d494a845acaf9db49ed2d2022-12-21T23:12:51ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022010-12-0112121031104010.1593/neo.10866ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease ProgressionDavid S. Rickman0Ying-bei Chen1Samprit Banerjee2Yihang Pan3Jindan Yu4Terry Vuong5Sven Perner6Christopher J. Lafargue7Kirsten D. Mertz8Sunita R. Setlur9Kanishka Sircar10Arul M. Chinnaiyan11Tarek A. Bismar12Mark A. Rubin13Francesca Demichelis14Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Public Health, Weill Cornell Medical College, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology, University of Michigan, Ann Arbor, MI, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADepartment of Pathology, MD Anderson Cancer Center, Houston, TX, USADepartment of Pathology, University of Michigan, Ann Arbor, MI, USADepartments of Pathology and Laboratory Medicine & Oncology, University of Calgary, Calgary, CanadaDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USATo 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.http://www.sciencedirect.com/science/article/pii/S1476558610800211 |
| spellingShingle | 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 ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression Neoplasia: An International Journal for Oncology Research |
| title | ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression |
| title_full | ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression |
| title_fullStr | ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression |
| title_full_unstemmed | ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression |
| title_short | ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression |
| title_sort | erg cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression |
| url | http://www.sciencedirect.com/science/article/pii/S1476558610800211 |
| work_keys_str_mv | AT davidsrickman ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT yingbeichen ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT sampritbanerjee ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT yihangpan ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT jindanyu ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT terryvuong ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT svenperner ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT christopherjlafargue ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT kirstendmertz ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT sunitarsetlur ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT kanishkasircar ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT arulmchinnaiyan ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT tarekabismar ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT markarubin ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression AT francescademichelis ergcooperateswithandrogenreceptorinregulatingtrefoilfactor3inprostatecancerdiseaseprogression |