Genetically Engineered Mouse Models of Prostate Cancer in the Postgenomic Era

Abstract

Recent genomic sequencing analyses have unveiled the spectrum of genomic alterations that occur in primary and advanced prostate cancer, raising the question of whether the corresponding genes are functionally relevant for prostate tumorigenesis, and whether such functions are associated with particular disease stages. In this review, we describe genetically engineered mouse models (GEMMs) of prostate cancer, focusing on those that model genomic alterations known to occur in human prostate cancer. We consider whether the phenotypes of GEMMs based on gain or loss of function of the relevant genes provide reliable counterparts to study the predicted consequences of the corresponding genomic alterations as occur in human prostate cancer, and we discuss exceptions in which the GEMMs do not fully emulate the expected phenotypes. Last, we highlight future directions for the generation of new GEMMs of prostate cancer and consider how we can use GEMMs most effectively to decipher the biological and molecular mechanisms of disease progression, as well as to tackle clinically relevant questions.