Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Oncogene. 2010 Feb 4;29(5):723-38. doi: 10.1038/onc.2009.373. Epub 2009 Nov 9.

C/EBPalpha redirects androgen receptor signaling through a unique bimodal interaction.

Author information

  • 1Department of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, OH 43614, USA.


Nuclear expression of CCAAT enhancer binding protein-alpha (C/EBPalpha), which supports tissue differentiation through several antiproliferative protein-protein interactions, augurs terminal differentiation of prostate epithelial cells. C/EBPalpha is also a tumor suppressor, but in many tumors its antiproliferative interactions may be attenuated by de-phosphorylation. C/EBPalpha acts as a corepressor of the classical androgen response element (ARE)-mediated gene activation by the androgen receptor (AR), but this is paradoxical as the genotropic actions of AR are crucial not only for the growth of the prostate but also for its maintenance and function. We show that DNA-bound C/EPBalpha recruits AR to activate transcription. C/EBPalpha-dependent trans-activation by AR also overrode suppression of AREs by C/EBPalpha elsewhere in a promoter. This mechanism was remarkable in that its androgen dependence was apparently for nuclear translocation of AR; it was otherwise androgen independent, flutamide insensitive and tolerant to disruption of AR dimerization. Gene response profiles and global chromatin associations in situ supported the direct bimodal regulation of AR transcriptional signaling by C/EBPalpha. This unique mechanism explains the functional coordination between AR and C/EPBalpha in the prostate and also shows that hormone-refractory AR signaling in prostate cancer could occur through receptor tethering.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk