Castration induces apoptosis in the ventral prostate but not in an androgen-sensitive prostatic adenocarcinoma in the rat

Abstract

Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma was studied during the post castration period of 14 days and compared with the ventral prostate. The mRNA expression of testosterone repressed prostatic message-2 and tissue-type plasminogen activator in the Dunning tumor and in the ventral prostate was analyzed by Northern blot experiments and immunohistochemical procedures. The degree of endonuclease-degraded genomic DNA was examined by gel electrophoresis. Apoptotic tumor epithelial cells were identified with in situ end labeling. Epithelial cells incorporating bromodeoxyuridine (BrdUrd) after castration in the ventral prostate and the Dunning tumors were localized with immunostaining. Androgen ablation resulted in an induction of testosterone repressed prostatic message-2 and tissue-type plasminogen activator transcripts in the normal prostate with a peak at approximately 2 to 5 days post castration. These transcript levels in the Dunning prostatic tumors did not show any induction during the same period. Immunohistochemical staining for sulfated glycoprotein-2 and tissue-type plasminogen activator confirmed this difference between the tumor tissue and the ventral prostate at the transcriptional level. The determination of DNA integrity showed similar results in that the degree of DNA fragmentation in the tumor was much lower than the initial and marked degradation of DNA in the ventral prostate. The number of in situ end-labeled epithelial tumor cells were not increased by castration. BrdUrd immunodetection showed that castration induced an initial increase in the number of BrdUrd-positive epithelial cells in the ventral prostate. In the tumors, castration resulted in a decrease in BrdUrd-positive epithelial cells. It was concluded that in the androgen-sensitive prostatic Dunning R3327 PAP adenocarcinoma, the biochemical cascade leading to apoptosis is not activated by androgen withdrawal, as in the ventral prostate.