The Role of B-Catenin in Androgen Receptor Signaling
Abstract
We have previously shown that the cell adhesion molecule beta-catenin can form a complex with the androgen receptor (AR) and modulate its transcription. The cross talk between 13-catenin and AR signaling can play an important, role in AR transcriptional in prostate cancer progression. The objective of this study is to determine the mechanisms by which beta-catenin modulates AR signaling. We show that beta-catenin can increase AR transcriptional activation, and can also restore the transcriptional activity of loss-of-function AR (507-919). We find that amino acid 716 is required for the interaction between AR and beta-catenin. To better understand AR-dependent transcription in vivo and the dynamics of AR/beta catenin interaction at gene promoters we used chromatin immunoprecipitation assays (ChIP assay) for the prostate-specific antigen (PSA) gene, the best- characterized androgen-responsive gene in the prostate gland. The results indicate that the dynamic loading of beta-catenin to the PSA promoter and enhancer shares the same pattern with AR in presence of dihydrotestosterone (DHT) and this loading is inhibited by the AR competitive antagonist, bicalutamide (Casodex). In the absence of DHT, bicalutamide can recruit both AR coactivators and corepressors to PSA gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA423750
Entities
People
- Cristina I. Truica
Organizations
- Vanderbilt University