CASTRATION PLUS ESTROGEN-TREATMENT INDUCES BUT CASTRATION ALONE SUPPRESSES EPITHELIAL-CELL APOPTOSIS IN AN ANDROGEN-SENSITIVE RAT PROSTATICADENOCARCINOMA

The positive effect of castration in prostatic cancer patients is cons idered to be related to the induction of apoptosis in androgen-depende nt tumour cells. However, castration apparently does not induce apopto sis in the highly differentiated, androgen-sensitive Dunning R3327PAP rat prostatic adenocarcinoma. To elucidate potential mechanisms of apo ptotic induction in this tumour model, rats with subcutaneously implan ted rumours were treated with vehicle (I), castration + vehicle (C) or castration + 50 pg of oestradiol benzoate per day s.c. (C + E2). The effects on rumours were examined by morphometry, in situ end labelling (ISEL) of apoptotic cells and immunohistochemically with monoclonal a ntibodies to proliferating cell nuclear antigen (PCNA) at different ti me points up to 168 h after castration. Castration inhibited tumour gr owth and decreased the epithelial cell apoptotic: rate (from 12 h) and epithelial cell proliferation rate (from 72 h) compared with that in the I group. Tumour volume, volume densities of epithelium and stroma and stroma cell proliferation rate remained constant in the C group du ring the study period. C + E2 treatment resulted in increases in cell proliferation in the stroma (from 12 h) and in the volume density of s troma (from 24 h) compared with that in the C and I groups. The number of apoptotic epithelial cells was increased (from 24 h), and this was followed by decreases in the volume density of epithelium (from 24 h) , the epithelial cell proliferation rate (from 72 h) and the total tum our volume (from 72 h). We conclude that in the Dunning R3327PAP tumou r model C + E2 treatment is more effective than castration alone. C E2 treatment, in contrast to C, is able to induce tumour cell death an d to decrease total tumour volume. The mechanism behind this effect is unknown, but it could be related to stimulatory effects of E2 in the tumour stroma.