Early castration-induced upregulation of transforming growth factor ?1 and its receptors is associated with tumor cell apoptosis and a major decline in serum prostate-specific antigen in prostate cancer patients
✍ Scribed by Wikstr�m, Pernilla; Westin, Patrick; Stattin, P�r; Damber, Jan-Erik; Bergh, Anders
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 728 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0270-4137
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✦ Synopsis
BACKGROUND.
The mechanism behind castration-induced apoptosis in prostate cells is unknown, but data from other species suggest that transforming growth factor 1 (TGF-1) may be involved. METHODS. By using quantitative RT-PCR and immunohistochemistry, expression of TGF-1 and its receptors type I and II (RI and RII) was studied in normal and tumor areas of core biopsies taken before and 2-11 days after castration therapy. The TGF- responses were related to changes in apoptotic index and to changes in serum prostate-specific antigen (PSA). RESULTS. In normal prostate tissue, apoptosis was generally increased by castration, and apoptosis was accompanied by an increase in TGF-1 and RII 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-1, RI, and RII mRNA levels were increased (P < 0.05). In the patients showing a prognostically favorable 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-1 and its receptors is associated with apoptosis in human prostate and prostate cancer, and possibly with a favorable clinical outcome after castration therapy.