AR-NcoR Interaction as a Therapeutic Target for Prostate Cancer Prevention and Treatment
Abstract
Aim 1 is to determine the precise molecular basis for NCoR binding to the RU486 liganded AR. Since the previous report we have used chromatin immunoprecipitation to demonstrate that RU486 enahnces AR NCoR recruitment to AR assembled on androgen regulated genes. We have also generated the additional AR and NCoR mutants to define the precise amino acids mediating the interaction. Aim 2 is to determine whether NCoR recruitment can suppress androgen independent expression of AR regulated genes and prostate cancer growth, and identify molecular markers that predict whether RU486 (or related drugs) will be effective in particular prostate cancers in vivo. We have now used chromatin immunoprecipitation to examine the functional effects of RU486 mediated NCoR recruitment, and find that NCoR is not mediating deacetylation and hence not suppressing gene expression. The reason for this is now under investigation. These results, in conjunction with our previous data, reflect further progress towards determining the structural basis for AR-NCoR interaction (Aim 1) and determining whether this interaction can be exploited to treat prostate cancer (Aim 2).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA463301
Entities
People
- Steven P Balk
Organizations
- Beth Israel Deaconess Medical Center