APOPTOSIS DURING CASTRATION-INDUCED REGRESSION OF THE PROSTATE IS FOSDEPENDENT

Apoptotic cell death was shown to be accompanied or preceded by an ele vated expression of the c-fos protooncogene and DNA binding activity o f transcription factor AP-1. We used Fos-deficient mice to study the r ole of c-Fos during programmed cell death in the prostate. In normal m ice apoptosis is induced in the prostate within 2-4 days after castrat ion. Histological features of reduced secretory activity and morpholog ical signs of programmed cell death become obvious. No apparent decrea se in secretory activity and no epithelial cell death were observed in Fos-deficient animals after castration. Fragmentation of nuclear DNA was measured by in situ terminal transferase reaction. DNA fragmentati on was observed in the prostate epithelium of control mice after castr ation whereas no similar fragmentation was found in Fos-deficient anim als. After castration an AP-1 complex accumulated in the prostate of F os deficient mice which mainly consists of FosB, Fra-2 and JunD wherea s in control animals the AP-1 complex in addition contained c-Fos. Our data strongly suggest that c-Fos is required for programmed cell deat h of prostate epithelial cells.