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Early castration‐induced upregulation of transforming growth factor β1 and its receptors is associated with tumor cell apoptosis and a major decline in serum prostate‐specific antigen in prostate cancer patients
Author(s) -
Wikström Pernilla,
Westin Patrick,
Stattin Pär,
Damber JanErik,
Bergh Anders
Publication year - 1999
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19990301)38:4<268::aid-pros2>3.0.co;2-4
Subject(s) - prostate cancer , medicine , downregulation and upregulation , apoptosis , receptor , prostate , prostate specific antigen , transforming growth factor , pca3 , tramp , antigen , castration , cancer research , oncology , cancer , immunology , biology , hormone , gene , biochemistry
BACKGROUND The mechanism behind castration‐induced apoptosis in prostate cells is unknown, but data from other species suggest that transforming growth factor β1 (TGF‐β1) may be involved. METHODS By using quantitative RT‐PCR and immunohistochemistry, expression of TGF‐β1 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‐β 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‐β1 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‐β1, 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‐β1 and its receptors is associated with apoptosis in human prostate and prostate cancer, and possibly with a favorable clinical outcome after castration therapy. Prostate 38:268–277, 1999. © 1999 Wiley‐Liss, Inc.