Publications

Abstract

?1 integrin is an extracellular matrix receptor that controls both normal and cancer cell phenotype in response to the local environment in a wide range of developmental systems. ?1 integrin expression is mis-localised during prostate cancer and has been shown to regulate acini formation in vitro. However, its role in prostate development and carcinogenesis remains unknown. To assess the role of ?1 integrin in normal prostate development and function, and a potential role in prostate carcinogenesis, we conditionally deleted ?1 integrin from prostate epithelium and subsequently crossed our ?1 integrin prostate-null mice to the TRAMP transgenic model of prostate carcinogenesis. Deletion of ?1 integrin did not perturb prostate morphology, but following castration and subsequent androgen supplementation, resulted in an expansion of the p63-positive basal cell population and decreased differentiation. Consistent with these findings, deletion of ?1 integrin in TRAMP mice resulted in an overall decrease in animal survival, decreased retention of normal prostate morphology and increased percentages of tissue with poorly differentiated carcinoma, which was associated with increased cell proliferation. This study demonstrates that ?1 integrin regulates several aspects of normal prostate development and in contrast to its role in several other tissues, its loss is associated with increased rates of prostate tumour progression.