Mechanism of RhoB/FTI Action in Breast Cancer
Abstract
Important progress was made this period on the important question of how FTI efficacy is achieved in breast cancer. Clinical trials have revealed that breast cancers respond to FTI but only in a minority of cases. What factors dictate FTI efficacy? Work completed earlier in this project defined rules for RhoB and its downstream effector kinase PRK in mediating growth inhibition by FTI in epithelial cells, including human breast epithelial cells. In this period, progress was made in identifying RhoB effectors that are implicated specifically in FTI-induced apoptosis, a process known to be critical for efficacy. Gene microarray studies identified modules that control cell division, MAPK signaling, and immune response as candidates (in press). We linked two genes that are Commonly dysregulated in breast cancer to apoptosis by FTI. Bini, an adapter-encoding gene implicated in breast cancer suppression, was shown to be essential for FTI-induced apoptosis (in press). Bini appears to act downstream of RhoB in apoptosis. Cyclin Bi, a key regulator of mitosis, is a critical target for RhoB suppression in FTI-induced apoptosis. We suggest that Bini loss and cyclin Bi overexpression, two events that occur commonly in breast cancer cells, may limit FTI efficacy in breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA419271
Entities
People
- George C. Prendergast
- Uma Kamasani