XIAP as a Molecular Target for Therapeutic Intervention in Prostate Cancer
Abstract
We have made very significant progress towards the completion of the goals proposed in this award. In the first of the two Aims, we proposed to generate cell lines in which we stably suppressed XIAP using lentiviral-based RNA interference, and subsequently to constitute XIAP expression using mutants which are incapable of suppressing caspases. While we have achieved these goals using PC-3 cells, we have encountered some issues of non-specificity when these lines are examined in xenograft models, and we are in the process of troubleshooting and examining alternative approaches to address these questions. In the second Aim, we proposed to examine XIAP expression in the TRAMP and Pten conditional transgenic murine models of prostate cancer. We have completed these studies in the TRAMP model, and found that surprisingly, there is little difference in the rates of tumor onset and the survival time of Xiap null mice, compared to littermate controls groups. Interestingly, there is a slight trend towards Xiap-deficient animals being more susceptible to tumors, which may have significant implications for the use of XIAP antagonists as anti-cancer agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA463464
Entities
People
- Colin S. Duckett
Organizations
- University of Michigan