Article: CDC25A functions as a novel AR corepressor in prostate cancer cells
| Title | CDC25A functions as a novel AR corepressor in prostate cancer cells | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Chiu, YT3 Han, HY3 Leung, SCL3 Yuen, HF2 Chua, CW Guo, Z1 Qiu, Y1 Chan, KW2 Wang, X3 Wong, YC3 Ling, MT3 | ||||||
| Issue Date | 2009 | ||||||
| Publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb | ||||||
| Citation | Journal of Molecular Biology, 2009, v. 385 n. 2, p. 446-456 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jmb.2008.10.070 | ||||||
| Abstract | Androgen receptor (AR) is a ligand-dependent transcription factor and its activity is regulated by numerous AR coregulators. Aberrant expression of AR coregulators in prostate cancer cells has an important role in the development and progression of prostate cancer. We report here that CDC25A, a cell cycle-promoting phosphatase over-expressed in a number of cancers, functions as an AR coregulator suppressing the AR transcriptional activity. In this study, we found that CDC25A is upregulated in human prostate cancer and its expression level is positively associated with the Gleason score and disease metastasis. More importantly, we showed that CDC25A can physically interact with AR through its putative catalytic domain. In addition, ectopic expression of CDC25A in prostate cancer cell lines suppresses PSA and Probasin promoter activities significantly, indicating that CDC25A may function as an AR corepressor. This was further confirmed by knockdown of endogenous CDC25A expression using small interfering RNA (siRNA), which resulted in upregulation of PSA promoter activity. Moreover, a truncated mutant that does not interact with AR fails to suppress the PSA promoter activity, indicating that CDC25A downregulates androgen-responsive promoter by physically interacting with AR. Taken together, our results demonstrated a novel function of CDC25A in the regulation of androgen signaling in human prostate cancer cells. | ||||||
| ISSN | 0022-2836 2011 Impact Factor: 4.001 2011 SCImago Journal Rankings: 0.728 | ||||||
| DOI | http://dx.doi.org/10.1016/j.jmb.2008.10.070 | ||||||
| ISI Accession Number ID | WOS:000262916900010
Funding Information: This work was supported by UGC seed funding to M.T. Ling (Seed funding programme for basic research, 2006) and by RGC grants to Y. C. W.g (HKU7470/04M and HKU foundation seed grant. | ||||||
| References | References in Scopus |
| dc.contributor.author | Chiu, YT | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Han, HY | ||||||
| dc.contributor.author | Leung, SCL | ||||||
| dc.contributor.author | Yuen, HF | ||||||
| dc.contributor.author | Chua, CW | ||||||
| dc.contributor.author | Guo, Z | ||||||
| dc.contributor.author | Qiu, Y | ||||||
| dc.contributor.author | Chan, KW | ||||||
| dc.contributor.author | Wang, X | ||||||
| dc.contributor.author | Wong, YC | ||||||
| dc.contributor.author | Ling, MT | ||||||
| dc.date.accessioned | 2012-05-29T06:13:58Z | ||||||
| dc.date.available | 2012-05-29T06:13:58Z | ||||||
| dc.date.issued | 2009 | ||||||
| dc.description.abstract | Androgen receptor (AR) is a ligand-dependent transcription factor and its activity is regulated by numerous AR coregulators. Aberrant expression of AR coregulators in prostate cancer cells has an important role in the development and progression of prostate cancer. We report here that CDC25A, a cell cycle-promoting phosphatase over-expressed in a number of cancers, functions as an AR coregulator suppressing the AR transcriptional activity. In this study, we found that CDC25A is upregulated in human prostate cancer and its expression level is positively associated with the Gleason score and disease metastasis. More importantly, we showed that CDC25A can physically interact with AR through its putative catalytic domain. In addition, ectopic expression of CDC25A in prostate cancer cell lines suppresses PSA and Probasin promoter activities significantly, indicating that CDC25A may function as an AR corepressor. This was further confirmed by knockdown of endogenous CDC25A expression using small interfering RNA (siRNA), which resulted in upregulation of PSA promoter activity. Moreover, a truncated mutant that does not interact with AR fails to suppress the PSA promoter activity, indicating that CDC25A downregulates androgen-responsive promoter by physically interacting with AR. Taken together, our results demonstrated a novel function of CDC25A in the regulation of androgen signaling in human prostate cancer cells. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Journal of Molecular Biology, 2009, v. 385 n. 2, p. 446-456 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jmb.2008.10.070 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.jmb.2008.10.070 | ||||||
| dc.identifier.epage | 456 | ||||||
| dc.identifier.hkuros | 203129 | ||||||
| dc.identifier.isi | WOS:000262916900010
Funding Information: This work was supported by UGC seed funding to M.T. Ling (Seed funding programme for basic research, 2006) and by RGC grants to Y. C. W.g (HKU7470/04M and HKU foundation seed grant. | ||||||
| dc.identifier.issn | 0022-2836 2011 Impact Factor: 4.001 2011 SCImago Journal Rankings: 0.728 | ||||||
| dc.identifier.issue | 2 | ||||||
| dc.identifier.pmid | 19013180 | ||||||
| dc.identifier.scopus | eid_2-s2.0-58149085157 | ||||||
| dc.identifier.spage | 446 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/148595 | ||||||
| dc.identifier.volume | 385 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | Journal of Molecular Biology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Androgen Receptor Antagonists | ||||||
| dc.subject.mesh | Androgen-Binding Protein - biosynthesis | ||||||
| dc.subject.mesh | Prostatic Neoplasms - physiopathology | ||||||
| dc.subject.mesh | Repressor Proteins - metabolism | ||||||
| dc.subject.mesh | cdc25 Phosphatases - metabolism | ||||||
| dc.title | CDC25A functions as a novel AR corepressor in prostate cancer cells | ||||||
| dc.type | Article |
Author Affiliations
- University of Maryland School of Medicine
- The University of Hong Kong
- Faculty of Medicine