Androgen‐mediated resistance to apoptosis

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Abstract
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.