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Article: CDC25A functions as a novel AR corepressor in prostate cancer cells

TitleCDC25A functions as a novel AR corepressor in prostate cancer cells
Authors
KeywordsAR
CDC25A
corepressor
prostate cancer
Issue Date2009
PublisherAcademic 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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/148595
ISSN
2023 Impact Factor: 4.7
2023 SCImago Journal Rankings: 2.212
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorChiu, YTen_HK
dc.contributor.authorHan, HYen_HK
dc.contributor.authorLeung, SCLen_HK
dc.contributor.authorYuen, HFen_HK
dc.contributor.authorChua, CWen_HK
dc.contributor.authorGuo, Zen_HK
dc.contributor.authorQiu, Yen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorLing, MTen_HK
dc.date.accessioned2012-05-29T06:13:58Z-
dc.date.available2012-05-29T06:13:58Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal of Molecular Biology, 2009, v. 385 n. 2, p. 446-456en_HK
dc.identifier.issn0022-2836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148595-
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.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmben_HK
dc.relation.ispartofJournal of Molecular Biologyen_HK
dc.subjectAR-
dc.subjectCDC25A-
dc.subjectcorepressor-
dc.subjectprostate cancer-
dc.subject.meshAndrogen Receptor Antagonistsen_US
dc.subject.meshAndrogen-Binding Protein - biosynthesisen_US
dc.subject.meshProstatic Neoplasms - physiopathologyen_US
dc.subject.meshRepressor Proteins - metabolismen_US
dc.subject.meshcdc25 Phosphatases - metabolismen_US
dc.titleCDC25A functions as a novel AR corepressor in prostate cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, SCL: steveell@hkucc.hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.emailLing, MT: patling@hkucc.hku.hk-
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.jmb.2008.10.070en_HK
dc.identifier.pmid19013180-
dc.identifier.scopuseid_2-s2.0-58149085157en_HK
dc.identifier.hkuros203129-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58149085157&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume385en_HK
dc.identifier.issue2en_HK
dc.identifier.spage446en_HK
dc.identifier.epage456en_HK
dc.identifier.isiWOS:000262916900010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridQiu, Y=8224645200en_HK
dc.identifier.scopusauthoridGuo, Z=42361137800en_HK
dc.identifier.scopusauthoridChau, CW=25930290600en_HK
dc.identifier.scopusauthoridYuen, HF=14018633400en_HK
dc.identifier.scopusauthoridLeung, SCL=36894169100en_HK
dc.identifier.scopusauthoridHan, HY=24477301600en_HK
dc.identifier.scopusauthoridChiu, YT=23975797700en_HK
dc.identifier.issnl0022-2836-

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