Transcription profiling of human LNCaP cells to investigate androgen receptor mediated gene expression by a sequence-specific DNA binding polyamide

ABSTRACT: Androgen Receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refractory disease. We have designed a sequence-specific DNA binding polyamide (1) that targets the consensus androgen response element (ARE). This polyamide binds the PSA promoter ARE, inhibits androgen-induced expression of PSA and several other AR-regulated genes in cultured prostate cancer cells, and reduces AR occupancy at the PSA promoter and enhancer. Down-regulation of PSA by this polyamide was comparable to that produced by the synthetic anti-androgen bicalutamide (Casodex) at the same concentration. Genome-wide expression analysis reveals that a similar number of transcripts are affected by treatment with the polyamide and with bicalutamide. Direct inhibition of AR-DNA binding by sequence-specific DNA binding small molecules could offer an alternative approach to antagonizing AR activity. A polyamide (2) that targets a different DNA sequence is included as a control. Experiment Overall Design: DHT (dihydrotestosterone)-stimulated LNCaP cells that were treatment with polyamide 1, polyamide 2, bicalutamide were compared to control cells that were also DHT-stimulated. Cells not stimulated with DHT were also compared to the DHT-stimulated controls. Three biological replicates were included for each treatment/condition except the no-DHT induced controls, which were in biological duplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Peter Dervan 

PROVIDER: E-GEOD-7708 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress