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Androgen-mediated resistance to apoptosis
Ronan N T Coffey1, R William G Watson, Amanda J O'Neill
1Department of Surgery, Mater Misericordiae Hospital, University College Dublin, Dublin, Ireland. research@profsurg.iol.ie
The Prostate
|November 14, 2002
Summary
Androgen (5-alphaDHT) protects prostate cancer cells from apoptosis by reducing pro-apoptotic gene expression. This survival effect is mediated by NF-kappaB, suggesting a general survival signaling role for androgens.
Area of Science:
- Molecular Biology
- Cancer Research
- Endocrinology
Background:
- Androgens exhibit a protective effect in prostate cancer cells (LNCaP).
- Mechanisms, especially androgen's impact on apoptosis-related gene expression, remain underexplored.
Purpose of the Study:
- Investigate androgen's influence on apoptotic sensitivity.
- Analyze androgen's effect on caspases and Bcl-2 family gene expression.
- Determine androgen's role in NF-kappaB activation.
Main Methods:
- Utilized LNCaP cell line for experiments.
- Assessed apoptosis following radiation and etoposide treatment.
- Examined gene expression of caspases and Bcl-2 family members.
- Employed gel mobility shift assay to study NF-kappaB activation.
Main Results:
- 5-alpha-Dihydrotestosterone (5-alphaDHT) conferred resistance to apoptosis induced by radiation and etoposide.
- This protection correlated with decreased expression of caspases and pro-apoptotic Bcl-2 family genes.
- 5-alphaDHT failed to protect NF-kappaB-inhibited LNCaP cells and androgen-insensitive cell lines (PC-3, DU-145).
Conclusions:
- 5-alphaDHT increases the apoptotic threshold in LNCaP cells by modulating pro-apoptotic gene expression.
- Androgen may act as a survival signal against various apoptotic pathways.
- NF-kappaB is hypothesized to be a key mediator in androgen-mediated survival signaling.