β1 integrin deletion enhances progression of prostate cancer in the TRAMP mouse model

Abstract

β1 integrin regulates the response of both normal and cancer cells to their local environment. Although mis-localised in prostate cancer, the role β1 integrin plays in prostate development and carcinogenesis remains unknown. To assess the role of β1 integrin in vivo, we conditionally deleted β1 integrin from prostate epithelium and subsequently crossed these mice to the TRAMP prostate carcinogenesis model. Deletion of β1 integrin 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 β1 integrin in TRAMP mice decreased animal survival, decreased retention of normal prostate morphology, increased the percentage of tissue with poorly differentiated carcinoma, and increased cell proliferation. This study demonstrates that β1 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.