The AIF/XIAP Axis in Prostate Cancer
Abstract
Over the funding period substantial progress was made towards completion of the project goals described in the original statement of work. AIF deficient PC3 cells were established and used to demonstrate that AIF does not affect the in vitro growth of these cells but is critical for growth of these cells in a xenograft model. These growth discrepancies manifest in both three dimensional cell culture growth and invasion assays, in which AIF was shown to be necessary for normal growth and invasion. Interestingly, three dimensional growth required the enzymatic activity of AIF, as an AIF variant lacking enzymatic activity failed to rescue cell growth in these cultures. Extending beyond our statement of work we have also shown that AIF ablation results directly in a loss of complex I of the mitochondrial electron transport chain with commensurate increases in cellular glycolytic activity. Noteably, while the enzymatic activity of AIF was not necessary to restore complex I protein levels, glycolytic levels remain elevated in all but the wildtype instance. Overall these data demonstrate for the first time a direct role for AIF in the progression of prostate cancer, and suggest that one mechanism that may explain this role is through control of mitochondrial energy production as a direct result of AIF enzymatic activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA554637
Entities
People
- John E. Wilkinson
Organizations
- Wake Forest University