Project description:Testosterone (20 mg) was subcutaneously adminstered to AR-97Q mice at postnatal day 1 (P1). Scramble-ASO and Rest4-ASO #3 were intracerebroventriculary administred to AR-97Q mice at P1.Gene expression profiles were analysed in the spinal cord of WT, AR-24Q, AR-97Q, testosterone-treated AR-97Q mice, Scramble-ASO-treated AR-97Q mice, and Rest4-ASO #3-treated AR-97Q mice at P7.
Project description:This study aimed at exploring how would the novel AR N-terminal inhibitor affect the androgen receptor (AR) transcriptome, especially a subset of genes that are uniquely upregulated by AR-V7 in castration resistant prostate cancer cells. We performed next-generation sequencing-based gene expression profiling (RNA-sequencing) on the castration-resistant prostate cancer celll line LNCaP-95. LNCaP-95 expresses high level of endogeneous AR-V7, and also acquired an adaptive shift towards AR-V7-mediated AR signaling activity. Beside regulating the transcription of a subset of canonical wildtype AR genes, AR-V7 also mediates a distinct transcriptional program that is independent of wildtype AR in LNCaP-95. In this experiment, LNCaP-95 cells were treated with vehicle control or the AR-N terminal inhibitor SC912. The subsequent AR transcriptomic change following compound treatment, especially the AR-V7 unique genes were assessed by RNA-seq.