Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. It is estimated that 30% of men over 50 years of age harbor foci of cancer in the prostate, which translates to an astounding 10 million affected individuals. New diagnostic and therapeutic approaches are needed to impact this steadily increasing health problem.

The key to understanding human health and disease may be found in the information stored within each cell of the human body as the digital DNA code comprising the genome. Studying the precise regulation of how this information is stored, replicated, and processed has the potential to identify the basic mechanisms that underlie the development of cancer. Methods have been developed that permit the examination of genes and their cognate proteins in exquisite detail, despite the microscopic nature and often transient existence of these molecules. Recent technological advances in the biomedical sciences now provide tools to begin to comprehensively examine the complex molecular events that occur in normal and cancerous prostate cells.

While great advances have been achieved by investigators studying individual molecules involved in cancer development, the work has been hampered by the lack of a complete "tool set" of all potential molecules that are relevant for understanding and defining the cancer process. This proposal aims to develop a virtual (computer-based) and physical "tool-set" of information and biological reagents for use by prostate-cancer researchers.

We have initiated this project by exploiting advances in biotechnology and informatics to establish a research tool termed the Prostate Expression Database (PEDB) (http://www.mbt.washington.edu/PEDB). PEDB is an integrated resource focused exclusively on prostate cancer that incorporates DNA sequences, protein sequences, and informatics resources suitable for analyzing these data. This proposal will extend PEDB development through the (1) detailed molecular analysis of specific cell and tumor types; (2) development of software tools and interfaces for investigator-initiated queries (expression, polymorphism identification, and gene regulation); and (3) assembly and distribution of a unique physical archive of genes expressed in the human prostate.

We envision that the approach described in this proposal will establish a molecular foundation and resource for identifying, studying, and obtaining prostate-specific and prostate cancer-associated molecules for detailed molecular, epidemiological, diagnostic, and therapeutic uses. This resource should extend our fundamental knowledge of normal and neoplastic cancer behavior and provide further avenues for diagnostic, prognostic, and therapeutic interventions.