The high prevalence of osteoblastic bone metastasis in prostate cancer is thought to be attributable to the production of osteoblast-stimulating factors by prostate cancer cells. Prostate-specific antigen (PSA) expression is arguably the most distinctive features of prostate cancer. PSA is a serine protease and an important serological marker for prostate cancer. Expression, secretion, and activation of transforming growth factor-beta (TGF-beta) is induced by PSA, and PSA-induced osteoblastic changes in bone were caused by an autonomous increase in mature osteoblasts and by depletion of the osteoclast population. Osteoblastic changes result from an imbalance between the rate of bone resorption and formation.