The Role of (BETA)-Catenin in Androgen Receptor Signaling
Abstract
Previously that the ceil adhesion molecule u-catenin forms a complex with the androgen receptor (AR) and modulate itstranscription. The cross talk between u-catenin and AR signaling can play an important role in AR transcriptional in prostatecancer progression. Our preliminary data seem indicate stromally derived paracrine Wnt family members activate theepithelial frizzled receptor to enable prostate epithelial survival in an androgen deficient environment. We will continue totest the original hypothesis that there is a direct molecular interaction between u-catenin and the 0-terminus region of ARinvolved in the mechanism of prostate androgen responsiveness. The physiologic response to androgen ablation(castration) differ significantly between the prostatic stroma and epithelia despite the common expression of u-catenin andAR as evidence for the different transcriptional cofactor interactions found in prostatic epithelial and stromal cells. Ourresults support the data that show u-catenin mutations enabling u-catenin stability in prostate cancer can lead to androgenindependence. At least two genetic interventions for hormonally refractive prostate cancer have emerged from our work: I) the expression of Hic-5 in the prostatic epithelia to inhibit canonical Wnt signaling and 2) antagonism of Wnt receptorlligandinteraction such as the expression of SFRP-2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA465851
Entities
People
- Neil A. Bhowmick
Organizations
- Vanderbilt University