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.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Chiu YT,Han HY,Leung SC,Yuen HF,Chau CW,Guo Z,Qiu Y,Chan KW,Wang X,Wong YC,Ling MTdoi
10.1016/j.jmb.2008.10.070subject
Has Abstractpub_date
2009-01-16 00:00:00pages
446-56issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(08)01370-3journal_volume
385pub_type
杂志文章abstract::R2 elements are non-long terminal repeat (non-LTR) retrotransposons with a single open reading-frame encoding reverse transcriptase, DNA endonuclease and nucleic acid-binding domains. The elements are specialized for insertion into the 28 S rRNA genes of many animal phyla. The R2-encoded activities initiate retrotrans...
journal_title:Journal of molecular biology
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