title: Suppression of metallothionein 3 gene expression by androgen in LNCaP prostate cancer cells.
abstract: 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). TheMT3gene 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 ofMT3and partially reversed the suppression ofMT3gene expression induced by DHT. In PC-3 cells lacking androgen receptors, DHT and bicalutamide exerted no effect onMT3gene expression. The reporter gene assay with a luciferase reporter plasmid containing the 5'-flanking region ofMT3demonstrated a decrease in luciferase activity caused by DHT that was reversed by bicalutamide. These results suggest thatMT3gene expression is downregulated by androgen.
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 501-1196, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 501-1196, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Hamada
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 501-1196, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iguchi
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 501-1196, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Usui
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Gifu 501-1196, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirano
keywords: LNCaP; androgen; metallothionein 3; prostate