Suppression of metallothionein 3 gene expression by androgen in LNCaP prostate cancer cells.

Androgen deprivation therapy is the standard treatment for prostate cancer. However, tumors often progress towards a more aggressive phenotype despite treatment. Prostate tissue has a high zinc concentration, which may correlate with prostate cancer progression. Therefore, we investigated the effect of dihydrotestosterone (DHT) on the gene expression of metallothioneins (MTs) and zinc transporters in prostate cancer with quantitative real-time polymerase chain reaction (PCR). The gene expression in LNCaP cells was suppressed by DHT in a dose-dependent manner. However, it increased in a culture medium containing androgen-deficient charcoal-stripped fetal bovine serum (FBS). Bicalutamide, an androgen receptor antagonist, increased the gene expression of and partially reversed the suppression of gene expression induced by DHT. In PC-3 cells lacking androgen receptors, DHT and bicalutamide exerted no effect on gene expression. The reporter gene assay with a luciferase reporter plasmid containing the 5'-flanking region of demonstrated a decrease in luciferase activity caused by DHT that was reversed by bicalutamide. These results suggest that gene expression is downregulated by androgen.