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Updated: Jun 18, 2026
09:07
Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
C/EBPalpha redirects androgen receptor signaling through a unique bimodal interaction
J Zhang1, M Gonit, M D Salazar
1Department of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, OH 43614, USA.
Oncogene
|November 11, 2009
Summary
CCAAT enhancer binding protein-alpha (C/EBPalpha) binds DNA to recruit the androgen receptor (AR), activating transcription. This novel mechanism explains prostate cell function and suggests hormone-refractory prostate cancer signaling via AR tethering.
Area of Science:
- Molecular biology
- Cell biology
- Oncology
Background:
- CCAAT enhancer binding protein-alpha (C/EBPalpha) promotes prostate epithelial cell differentiation and acts as a tumor suppressor.
- C/EBPalpha can attenuate its antiproliferative effects through de-phosphorylation in tumors.
- C/EBPalpha paradoxically acts as a corepressor for androgen receptor (AR)-mediated gene activation, despite AR's importance in prostate function.
Purpose of the Study:
- To elucidate the paradoxical role of C/EBPalpha as both a tumor suppressor and a corepressor of AR signaling.
- To investigate the mechanism by which C/EBPalpha regulates AR-mediated transcription in prostate cells.
- To explore the implications of this regulatory mechanism in prostate cancer progression and hormone resistance.
Main Methods:
- Investigated C/EBPalpha and AR interactions using in vitro and in situ techniques.
- Analyzed gene expression profiles and global chromatin associations.
- Assessed the functional consequences of C/EBPalpha-AR complex formation on androgen response element (ARE) activity.
Main Results:
- DNA-bound C/EBPalpha recruits AR to activate transcription, overriding its suppressive effects on AREs.
- This C/EBPalpha-dependent trans-activation by AR is androgen-independent, flutamide-insensitive, and resistant to AR dimerization disruption.
- Gene expression and chromatin data confirm direct, bimodal regulation of AR signaling by C/EBPalpha.
Conclusions:
- A novel mechanism reveals C/EBPalpha directly regulates AR transcriptional activity, coordinating AR and C/EBPalpha function in the prostate.
- This interaction provides a potential explanation for hormone-refractory AR signaling in prostate cancer through AR tethering.
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