Role of the ARF Tumor Suppressor in Prostate Cancer

摘要

The nucleolar 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. We have been unable to obtain a pure mouse prostate epithelial cell culture, therefore, we have taken two alternative approaches. First, we will knockdown basal ARF levels 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 allow us to monitor polysome mRNA association in the absence of ARF. While we have encountered difficulties over the course of this two-year award, we have developed these new techniques to allow the research project to progress toward the approved goal of biomarker development and have applied for additional funding to continue the project.