XIAP as a Molecular Target for Therapeutic Intervention in Prostate Cancer
Annual rept. 23 Sep 2004-22 Sep 2005
MICHIGAN UNIV ANN ARBOR
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We have made major 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. We have achieved this goal in PC-3 cells, and are well underway to generating similar clones in the three other cell lines we originally proposed. The first round of PC-3 derivatives have been injected into nude mice and we have exciting preliminary data supporting a role for XIAP in oncogenesis, and validating our model system for dissecting the properties of XIAP. In the second Aim, we proposed to examine XIAP expression in the TRAMP and Pten conditional transgenic murine models of prostate cancer. We have made great progress in the TRAMP system, and generated breeding colonies of Xiap-deficient, TRAMP mice. Finally, our studies to evaluate the effectiveness of a murine, XIAP-specific antisense oligonucleotide are now underway in TRAMP mice.
- Anatomy and Physiology
- Medicine and Medical Research