title: CDC25A functions as a novel Ar corepressor in prostate cancer cells.
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.
authors.affiliation: Cancer Biology Group, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China.
authors.forename: Yung-Tuen
authors.initials: YT
authors.lastname: Chiu
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Han
authors.forename: Steve Chin-Lung
authors.initials: SC
authors.lastname: Leung
authors.forename: Hiu-Fung
authors.initials: HF
authors.lastname: Yuen
authors.forename: Chee-Wai
authors.initials: CW
authors.lastname: Chau
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Xianghong
authors.initials: X
authors.lastname: Wang
authors.forename: Yong-Chuan
authors.initials: YC
authors.lastname: Wong
authors.forename: Ming-Tat
authors.initials: MT
authors.lastname: Ling
mesh_terms: D059002:Androgen Receptor Antagonists; D000727:Androgen-Binding Protein / Q000096:biosynthesis; D002460:Cell Line; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism*
chemical_list: D059002:Androgen Receptor Antagonists; D000727:Androgen-Binding Protein; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C027519:probasin; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D017430:Prostate-Specific Antigen