[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.