Prostate cancer represents a serious health problem for American men since it represents the second leading cause of cancer death in men, and it is estimated that one out of every nine men will develop prostate cancer. Therefore, it is necessary to spend considerable effort to understand why prostate cancer occurs and why it is on the rise. If we obtain a better understanding of the molecular pathway that leads to prostate cancer, we will be in a better position to find more rational strategies for prevention and treatment of this disease.

Researchers have made excellent progress in understanding the causes of other types of cancers by developing animal model systems. Often it is the case that models for cancer are developed in mice because they are amenable to genetic manipulation. These mouse models have allowed researchers to follow the pathway that leads to a particular type of cancer, and to understand how various molecules can work together to halt or promote the cancer process.

Until now, it has been difficult to develop a model system for prostate cancer because there have been few molecules that are "candidates" in the pathway that leads to prostate cancer. We have now identified a molecule, termed Nkx3.1, that we believe to be lost as one of the first steps in the pathway to prostate cancer. Thus, we find that Nkx3.1 is important for the healthy prostate and, if Nkx3.1 is not able to function, the prostates begin to take on a cancer-like appearance.

These observations were made using a mouse model that we developed in which Nkx3.1 is no longer able to function (called Nkx3.1 mutant mice). The goal of this proposal is to build upon these Nkx3.1 mutant mice to ask about the role of other molecules that may be downstream of Nkx3.1 in the pathway to prostate cancer. Therefore, these proposed studies represent a unique opportunity to develop a model for prostate cancer that will help us to unravel the events that lead to this disease.