Chemotherapy, hormonal
therapy, or surgery may cause devastating toxic or other side effects.
Androgen receptors (ARs) in the cytoplasm are activated by binding with
androgen.
Androgen-activated ARs bind to a specific genomic DNA sequence, the
androgen-responsive
element (ARE), and initiate gene expression at the transcriptional level. Even without
androgen activation, ARs may have a role in
androgen-refractory
prostate cancer. Thus, inhibition of AR activity may have therapeutic value. We applied a genetic reporter of the Dual-
Luciferase Assay System to test whether a short double-stranded genomic
DNA containing
prostate-specific antigen (PSA) ARE sequence as decoy
DNA would inhibit the function of activated AR. A 21-mer phosphorothioated PSA ARE decoy
DNA was synthesized, with a plasmid vector containing the PSA promoter upstream from a
luciferase gene, the reporter gene. The promoter and reporter were co-transfected into a human
prostate cancer cell line PC3-M with the aid of Lipofectamin 2000. After 24 hr exposure to
androgens, the cells were lysed and
luciferase activity measured to determine the ARE decoy inhibitory effect on the function of ARs.
Luciferase activity was reduced significantly in the ARE decoy transfected cells but not with inactive control decoy. The results demonstrate that ARE decoy
DNA can effectively suppress
androgen-activated ARs in
prostate cancer cells and indicate the potential utility of decoy
DNA for developing a novel
therapy for
prostate cancer.