Androgen‐mediated resistance to apoptosis
2002; Wiley; Volume: 53; Issue: 4 Linguagem: Inglês
10.1002/pros.10159
ISSN1097-0045
AutoresRonan N. T. Coffey, R. William G. Watson, Amanda O’Neill, Kevin Mc Eleny, John M. Fitzpatrick,
Tópico(s)Prostate Cancer Treatment and Research
ResumoAbstract BACKGROUND Previous studies demonstrate that androgen is capable of exerting a protective effect in the androgen‐sensitive human prostate cancer cell line LNCaP. Limited studies, however, have addressed the underlying mechanisms involved, in particular the effects of androgen on both pro‐ and anti‐apoptotic gene expression. METHODS We investigated the effects of androgen on apoptotic sensitivity and the expression of the caspases and specific members of the Bcl‐2 family in the LNCaP cell line. The effects of androgen on NF‐κB activation were also investigated by using a gel mobility shift assay. RESULTS 5α‐Dihydrotestosterone (5‐αDHT) conferred resistance to radiation (5 Gy) and etoposide‐induced apoptosis in the LNCaP cell line. This finding was associated with a time‐dependent decrease in the expression of the caspases and pro‐apoptotic Bcl‐2 family members. 5‐αDHT did not confer protection against apoptosis in the LNCaP line transfected with the IκB super repressor of NF‐κB, nor in the androgen insensitive PC‐3 and DU‐145 cell lines. CONCLUSION The ability of 5‐αDHT to raise the apoptotic threshold in the LNCaP cell line by altering specific pro‐apoptotic gene expression suggests that androgen may serve as a general survival signal against diverse pathways that ultimately signal for apoptosis. We hypothesize that NF‐κB serves as an important mediator in androgen survival signaling. Prostate 53: 300–309, 2002. © 2002 Wiley‐Liss, Inc.
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