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Apoptosis during castration-induced regression of the prostate is Fos dependent
1Institute of Molecular and Cell Biology, National University of Singapore, Singapore.
Abstract:
Apoptotic cell death was shown to be accompanied or preceded by an elevated expression of the c-fos protooncogene and DNA binding activity of transcription factor AP-1. We used Fos-deficient mice to study the role of c-Fos during programmed cell death in the prostate. In normal mice apoptosis is induced in the prostate within 2-4 days after castration. Histological features of reduced secretory activity and morphological signs of programmed cell death become obvious. No apparent decrease 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 fragmentation was observed in the prostate epithelium of control mice after castration whereas no similar fragmentation was found in Fos-deficient animals. After castration an AP-1 complex accumulated in the prostate of Fos deficient mice which mainly consists of FosB, Fra-2 and JunD whereas in control animals the AP-1 complex in addition contained c-Fos. Our data strongly suggest that c-Fos is required for programmed cell death of prostate epithelial cells.
Insights
The protooncogene c-Fos is essential for programmed cell death in the prostate. Fos-deficient mice lack castration-induced apoptosis, indicating c-Fos
Area of Science:
- Cell Biology
- Oncology
- Molecular Biology
Background:
- Apoptotic cell death is linked to c-Fos protooncogene expression and AP-1 transcription factor activity.
- Programmed cell death plays a critical role in prostate homeostasis and involution.
Purpose of the Study:
- To investigate the role of c-Fos in prostate epithelial cell apoptosis following castration.
- To elucidate the molecular mechanisms underlying c-Fos-mediated programmed cell death.
Main Methods:
- Utilized Fos-deficient mice and wild-type littermates for comparative analysis.
- Induced apoptosis via castration in experimental animals.
- Assessed histological changes, secretory activity, and epithelial cell death.
- Quantified nuclear DNA fragmentation using in situ terminal transferase reaction.
- Analyzed AP-1 transcription factor complex composition via Western blotting or similar techniques.
Main Results:
- Castration induced significant apoptosis and reduced secretory activity in wild-type mice.
- Fos-deficient mice exhibited no significant decrease in secretory activity or epithelial cell death post-castration.
- Nuclear DNA fragmentation, a hallmark of apoptosis, was observed in wild-type but not Fos-deficient prostates.
- AP-1 complexes in Fos-deficient mice primarily comprised FosB, Fra-2, and JunD, lacking c-Fos, unlike control animals.
Conclusions:
- c-Fos is indispensable for initiating programmed cell death in prostate epithelial cells after castration.
- The absence of c-Fos prevents castration-induced apoptosis and maintains prostate epithelial cell viability.
- These findings highlight c-Fos as a key regulator of prostate involution and a potential therapeutic target.