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Cancer Lett. 2007 Aug 28;254(1):137-45. Epub 2007 Apr 12.

14-3-3 sigma increases the transcriptional activity of the androgen receptor in the absence of androgens.

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Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.


The androgen receptor (AR) is a ligand-activated transcription factor that regulates numerous target genes, including prostate-specific antigen (PSA). We examined the ability of each member of the 14-3-3 family to modulate transcription of PSA through the AR. Despite significant homology within the 14-3-3 family we observed differences in the ability of each isoform to alter the transcriptional activity of the AR. Significantly, 14-3-3 sigma activated PSA-luciferase reporters not only at castrate levels of androgens, but also in the complete absence of androgens. 14-3-3 sigma also increased expression of the endogenous PSA gene in the absence of androgens. Knockdown of the AR by siRNA oligonucleotides abolished activation of these reporters by 14-3-3 sigma. These findings may have greatest significance in hormone refractory prostate cancer where the AR may be activated in a ligand-independent manner.

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