ESTROGEN INDUCES APOPTOSIS IN A RAT PROSTATIC ADENOCARCINOMA - ASSOCIATION WITH AN INCREASED EXPRESSION OF TGF-BETA-1 AND ITS TYPE-I AND TYPE-II RECEPTORS

Rats transplanted with the androgen-sensitive Dunning R3327 PAP prosta tic adenocarcinoma were castrated and treated with either estrogen or vehicle alone for short periods (4 hr, 12 hr, 24 hr) and for 6 weeks. In these tumors the expression of TGF-beta 1, TGF-beta type-I and type -II receptors (TGF-beta RI, TGF-beta RII) was examined by immunohistoc hemistry. Apoptotic cells were identified by in situ nick end labellin g (TUNEL). Tumor growth was retarded by castration and even more by ad ditive estrogen treatment. The epithelium of the untreated tumors stai ned weakly for TGF-beta 1 and TGF-beta RI, but TGF-beta RII was not de tected. Castration induced moderate TGF-beta 1 immunoreactivity in a m ajor part of the glandular epithelium after 24 hr. After 12 hr already , castration plus estrogen resulted in an intense staining for TGF-bet a 1 in the basal epithelial cells, some of which also showed an apopto tic appearance. The percentage of cells having stained positive for TG F-beta 1 was significantly higher in the estrogen-treated groups than in the castrated group after 12 hr, and its elevated TGF-beta 1 level remained at 6 weeks. Notably, the increased immunoexpression of TGF-be ta 1 occurred before the onset of induction of apoptosis. In parallel with the upregulation of TGF-beta 1 after castration, the expression o f its receptors, TGF-beta RI and RII, was induced and was further enha nced by the additive estrogen treatment. The number of intensely stain ed TGF-beta 1 tumor cells showed a strong correlation with the number of apoptotic tumor cells identified by TUNEL in the whole material. Fu rthermore, TGF-beta 1 immunoreactivity co-localized with the presence of apoptotic cells in the estrogen-treated tumors at 6 weeks after cas tration. (C) 1996 Wiley-Liss, Inc.