Role of the ARF Tumor Suppressor in Prostate Cancer
Abstract
The nucleolar tumor suppressor ARF plays an important role in the tumor surveillance of human cancer. We have found that ARF expression is absence from highly proliferative prostate adenocarcinomas and this correlates with the increased expression of the p53-independent target of NPM. We have created and characterized an immortalized ARF-null Prostate Epithelial cell line. In addition we have shown that alterations in NPM levels can have dramatic affects on the androgen-dependent cancer cell line, LNCaP, but PC3 cells which are androgen-independent. We have previously shown that ARF inhibits NPM's nuclear export and cell cycle progression in a p53-independent manner. Under this proposal we have defined the mechanism by which this happens. Specifically, ARF binds to NPM preventing its ability to carry both small and large ribosomal subunits out of the nucleus. This results in a decrease in protein synthesis and growth rates contributing to ARF s tumor suppressor function. We are beginning to further define the role of ARF in prostate cell growth. These studies are opening the door to new therapeutic targets in prostate cancer; namely protein synthesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA456845
Entities
People
- Leonard Maggi Jr.
Organizations
- Washington University in St. Louis