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Article: CDC25A functions as a novel AR corepressor in prostate cancer cells
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TitleCDC25A functions as a novel AR corepressor in prostate cancer cells
 
AuthorsChiu, YT3
Han, HY3
Leung, SCL3
Yuen, HF2
Chua, CW
Guo, Z1
Qiu, Y1
Chan, KW2
Wang, X3
Wong, YC3
Ling, MT3
 
Issue Date2009
 
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb
 
CitationJournal 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
 
AbstractAndrogen 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.
 
ISSN0022-2836
2013 Impact Factor: 3.959
2013 SCImago Journal Rankings: 3.158
 
DOIhttp://dx.doi.org/10.1016/j.jmb.2008.10.070
 
ISI Accession Number IDWOS:000262916900010
Funding AgencyGrant Number
UGC
RGCHKU7470/04M
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChiu, YT
 
dc.contributor.authorHan, HY
 
dc.contributor.authorLeung, SCL
 
dc.contributor.authorYuen, HF
 
dc.contributor.authorChua, CW
 
dc.contributor.authorGuo, Z
 
dc.contributor.authorQiu, Y
 
dc.contributor.authorChan, KW
 
dc.contributor.authorWang, X
 
dc.contributor.authorWong, YC
 
dc.contributor.authorLing, MT
 
dc.date.accessioned2012-05-29T06:13:58Z
 
dc.date.available2012-05-29T06:13:58Z
 
dc.date.issued2009
 
dc.description.abstractAndrogen 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.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal 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.doihttp://dx.doi.org/10.1016/j.jmb.2008.10.070
 
dc.identifier.epage456
 
dc.identifier.hkuros203129
 
dc.identifier.isiWOS:000262916900010
Funding AgencyGrant Number
UGC
RGCHKU7470/04M
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.issn0022-2836
2013 Impact Factor: 3.959
2013 SCImago Journal Rankings: 3.158
 
dc.identifier.issue2
 
dc.identifier.pmid19013180
 
dc.identifier.scopuseid_2-s2.0-58149085157
 
dc.identifier.spage446
 
dc.identifier.urihttp://hdl.handle.net/10722/148595
 
dc.identifier.volume385
 
dc.languageeng
 
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofJournal of Molecular Biology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAndrogen Receptor Antagonists
 
dc.subject.meshAndrogen-Binding Protein - biosynthesis
 
dc.subject.meshProstatic Neoplasms - physiopathology
 
dc.subject.meshRepressor Proteins - metabolism
 
dc.subject.meshcdc25 Phosphatases - metabolism
 
dc.titleCDC25A functions as a novel AR corepressor in prostate cancer cells
 
dc.typeArticle
 
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<contributor.author>Chua, CW</contributor.author>
<contributor.author>Guo, Z</contributor.author>
<contributor.author>Qiu, Y</contributor.author>
<contributor.author>Chan, KW</contributor.author>
<contributor.author>Wang, X</contributor.author>
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Author Affiliations
  1. University of Maryland School of Medicine
  2. The University of Hong Kong
  3. Faculty of Medicine