Models of metastatic prostate cancer: a transgenic perspective

Purpose: Transgenic mouse models are proving to be invaluable in our effort to understand the molecular basis of metastatic prostate cancer (CaP). We review and discuss how current animal models have contributed to our understanding of the metastatic cascade and how transgenic technology is being used to develop the next generation of mouse models. Our goal is to provide a review of the recent advances and provide a framework for further studies. Materials and Methods: We performed a MEDLINE search of the literature on CaP metastasis transgenic and animal models. Results: We present a summary of the characteristics of nine different animal models of CaP. Each model is unique and provides valuable insight into the molecular mechanisms governing the progression of CaP. Our experience with transgenic models and all the new data from the literature predicts that we will be able to develop genetically engineered mice that accurately mimic the heterogeneity, androgen-independent growth, and metastatic spread seen in clinical disease. Conclusion: In order to elucidate the molecular mechanisms of CaP metastasis, it will be necessary to compare gene and protein expression patterns and biochemical analyses of clinical metastatic disease with data obtained from current models. We will also need to refine our ability to engineer and characterize genetic perturbation models. This type of integrative and iterative approach should facilitate better understanding of the molecular biology of CaP metastases.