Prostate Cancer Gene Expression Changes after Treatment with Neoadjuvant Dutasteride

To identify molecular changes underlying the chemopreventive or tumor promoting effects of SRD5A inhibition, we profiled gene expression changes in benign prostate epithelium from patients with PCa treated with dutasteride, a dual SRD5A inhibitor. Subjects were aged 45-80 years with clinically localized PCa (T1C to T2b), Gleason score <7, and serum PSA 2.5-10 ng/dL. 81 men were randomized to immediate RP (n=25) or to dutasterdie at 0.5 mg (n=26) or 3.5 mg (n=24) orally per day for four months prior to RP. Prostate samples embedded in OCT were used for laser capture microdissection (LCM). Keywords: clinical trial, Dutasteride, PEDB, dose response, prostate cancer, microarray Subjects were aged 45-80 years with clinically localized PCa (T1C to T2b), Gleason score <7, and serum PSA 2.5-10 ng/dL. 81 men were randomized to immediate RP (n=25) or to dutasterdie at 0.5 mg (n=26) or 3.5 mg (n=24) orally per day for four months prior to RP. Prostate samples embedded in OCT were used for laser capture microdissection (LCM). Approximately 2000-3000 epithelial cells per sample were collected from 8µm sections using the Arcturus Veritas™ Laser Capture Microdissection System according to the Arcturus HistoGene LCM Frozen Section Staining Kit Protocol (Mountain View, CA). Total RNA was isolated using the Arcturus Picopure™ Kit, and the samples were treated with DNAse using the Qiagen RNase-Free DNase Set (Qiagen Inc, Valencia, CA). Total RNA was subjected to two rounds of linear amplification using the Ambion MessageAmpII Kit (Ambion Inc, Austin, TX), quantitated in a Gene-Spec III spectrophotometer (Hitachi, Tokyo) and aRNA integrity evaluated using gel electrophoresis. 40 Human Prostate (PEDB) Microarrays were run with sample on the Cy3 channel against a Human Gold Standard (v5) on the Cy5 channel.