[Expression and regulation of androgen receptor in the androgen-independent conversion of prostate cancer cells].

OBJECTIVE: To investigate the expression and regulation of androgen receptor (AR) in prostate cancer cells from androgen dependent to androgen independent. METHODS: LNCaP cells were cultured in charcoal-stripped serum for 6 months to establish androgen-independent celline (LNCaP-AI). Proliferation of LNCaP-AI was assayed by cell viability. Expression of AR mRNA and protein was analyzed by RT-PCR and Western blot. Wnt signaling pathway inhibitor IWR-1 and proteasome inhibitor lactacystin were used to investigate effects of Wnt and proteasome pathway on AR expression in LNCaP-AI. RESULTS: LNCaP-AI exhibit enhanced proliferation and up-regulated PSA expression compared with LNCaP. During androgen deprivation, AR mRNA was up-regulated in a short early stage and then declined to a stable level in LNCaP-AI compared with LNCaP, but AR protein kept in downward trend. The mRNA and protein expression of AR was decreased by IWR-1 treatment. AR protein but not mRNA was increased by lactacystin treatment. CONCLUSION: The androgen independent prostate cancer cell line was established by androgen deprivation, in which the protein expression of AR was dramatically decreased. mRNA and protein expression of AR in LNCaP-AI was related to Wnt signaling pathway and proteasome pathway. Increased Wnt signaling or decreased proteasome pathways contribute the decreased AR protein expression.