Early castration-induced upregulation of transforming growth factor beta 1and its receptors is associated with tumor cell apoptosis and a major decline in serum prostate-specific antigen in prostate cancer patients

BACKGROUND. The mechanism behind castration-induced apoptosis in prostate c ells is unknown, but data from other species suggest that transforming grow th factor beta 1 (TGF-beta 1) may be involved. METHODS. By using quantitative RT-PCR and immunohistochemistry, expression of TGF beta 1 and its receptors type I and II (RI and RII) was studied in n ormal and tumor areas of core biopsies taken before and 2-11 days after cas tration therapy. The TGF-beta responses were related to changes in apoptoti c index and to changes in serum prostate-specific antigen (PSA). RESULTS. In normal prostate tissue, apoptosis was generally increased by ca stration, and apoptosis was accompanied by an increase in TGF-beta 1 and RI I mRNA levels (P < 0.05). In tumors, apoptosis was seen only in 44% of the cases and in these, but not in the others, TGF-beta 1, RI, and RII mRNA lev els were increased (P < 0.05). In the patients showing a prognostically fav orable PSA response (nadir PSA <5 ng/ml), but not in the others, RI and RII mRNA levels were significantly upregulated (P < 0.05). CONCLUSIONS. Short-term upregulation of TGF-beta 1 and its receptors is ass ociated with apoptosis in human prostate and prostate cancer, and possibly with a favorable clinical outcome after castration therapy. (C) 1999 Wiley- Liss, Inc.