ABSTRACT
It is estimated that prostate cancer will be the most diagnosed of all human cancers in 2005 and will continue to remain the second leading yearly cause of cancer related deaths amongst men in the United States (American Cancer Society, Facts and Figures; www.cancer.org). Despite considerable research effort, the underlying causes of prostate cancer remain elusive, and, therefore, we have yet to appreciably influence the efficacy of current therapeutic intervention strategies aimed towards preventing or treating advanced disease.1-3
Prostate cancer is a disease mostly unique to aging men, and our understanding of the natural history of prostate cancer remains uncertain, in part, because of the heterogeneous nature of both the disease and the patient population. It is generally accepted, however, that prostate cancer progresses slowly, originating from focal hyperplasias or atrophic inflammatory regions representing early-stage disease through low-and highgrade prostatic epithelial neoplasia (PIN) lesions to become adenocarcinomas that can metastasize to distant sites, most notably to bone. Similar to most if not all cancer, genetic alterations are likely requisite for initiation and progression to advanced disease.4
Interestingly, many of the well-known and characterized tumor susceptibility genes are not mutated with high frequency in prostate tumors. Rather, prostate tumors appear to exhibit tremendous diversity in identifiable genetic lesions both between and within individual tumors5 (recently reviewed by several authors6-8). It has, therefore, been challenging to identify and isolate clinically relevant prostate cancer tumor susceptibility genes and to develop appropriate and valid models that
