Transforming growth factor-beta 1 and prostate cancer

Transforming growth factor-beta 1 (TGF-beta 1) is an important regulator of the normal and malignant prostate. In the non-malignant prostate, TGF-beta 1 stimulates cell differentiation, inhibits epithelial cell proliferation and induces epithelial cell death. TGF-beta 1 is secreted into semen and he re it is an important immunosuppressive factor. Prostate cancer cells expre ss high levels of TGF-beta 1 and it seems to enhance prostate cancer growth and metastasis by stimulating angiogenesis and by inhibiting immune respon ses directed against tumour cells. Prostate cancer cells frequently lose th eir TGF-beta receptors and acquire resistance to the anti-proliferative and pro-apoptotic effects of TGF-beta I. Accordingly, high expression of TGF-b eta 1 and loss of TGF-beta receptor expression have been associated with a particularly bad prognosis in human prostate cancer patients. TGF-beta 1 al so seems to be a mediator of castration-induced apoptosis in androgen depen dent normal and malignant prostate epithelial cells. The ability of some pr ostate tumours to avoid castration-induced apoptosis is however not simply due to loss of TGF-beta receptor type I or II expression in the tumour tell s, but may also be related to an inability of these cells to up-regulate TG F-beta receptor levels in response to castration or possibly due to defects downstream of the receptors. Short-term therapy-induced changes in the TGF -beta system in prostate tumours can probably be used to predict the long-t erm response to androgen ablation treatment. Further investigations into th e TGF-beta system in the prostate are, however, needed to elucidate how alt erations in this system affect the behaviour of prostate tumours, and if th is system can be manipulated for therapeutical purposes.