Role of the ARF Tumor Suppressor in Prostate Cancer
Abstract
The nuclear tumor suppressor ARF plays an important role in the tumor surveillance of human cancer. We have found that ARF expression is absent from highly proliferative prostate adenocarcinomas. This correlates with the normal expression of the p53 tumor suppressor gene indicating that ARF loss could be a contributing factor for prostate cancer initiation and/or progression. We have found that ARF-mull mice develop prostatic lesions by 9 months of age (2/10), but die of sarcoma or lymphoma. We have generated and are monitoring prostate specific ARF and ARF/p53 knockout animals for the development of prostate lesions avoiding the complication of genomic loss of these tumor suppressors. While our mouse prostate epithelial cultures have not grown well, we have taken two additional approaches to assess ARF's role in prostate growth control. First, we have lentiviral shRNA constructs which can knockdown basal ARF levels for use in commercially available normal human prostate epithelial cell lines. Second, we have developed a protocol to isolate polysomes from freshly isolated whole mouse prostates. Both of these techniques will allow us to monitor polysome mRNA association in the absence of ARF. While we have encountered difficulties in this first year, we have developed new techniques to allow the research project to progress toward the approved goal of biomarker development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA541881
Entities
People
- Adam S. Kibel
- Leonard B. Maggi Jr.
Organizations
- Washington University in St. Louis