Hedgehog signaling in prostate growth and benign prostate hyperplasia

Abstract

Hedgehog (Hh) signaling has long been recognized for its role in axial patterning, mesenchymal-epithelial inductive signaling, and growth regulation during fetal development. In many embryonic tissues, Hh functions as a proliferative stimulus. Sonic hedgehog and Indian hedgehog are both expressed by the urothelium of the fetal prostate anlage, where they regulate cell proliferation and differentiation and play a role in prostate ductal budding. Whereas Hh signaling in mouse prostate diminishes during adolescence and is maintained at a low level in the adult, robust Hh signaling is commonly found in the adult human prostate. The reason(s) for robust Hh signaling in the adult human prostate and the actions of Hh signaling on growth and differentiation in the adult are not well understood. However, increased Hh signaling has been associated with prostate cancer and has been shown to accelerate prostate cancer growth. These observations suggest that inappropriate reawakening of this developmental growth signal may play a pivotal role in prostate neoplasia. This review examines the role of Hh signaling during early prostate growth and in its corollary actions during prostate disease, including benign prostate hyperplasia and prostate cancer. The use of Hh inhibitors as a therapeutic modality for androgen-independent treatment of prostate disease is also discussed.