关键词：雄激素；前列腺癌；受体位点（生理学）；医药
摘 要：Recent data indicate that castration-recurrent prostate cancer (CR- CaP) progression is driven by the activation of wild-type androgen receptor (AR) through at least two mechanisms: tyrosine phosphorylation by Src family (SFK) and Ack1 tyrosine kinases, and the induction of AR coregulators that regulate the transcriptional activity of AR. It is likely that identifying novel AR-regulated genes in CR-CaP, especially those involving promoters with novel target sequences, will help elucidate the molecular mechanisms that drive CR-CaP initiation and progression, and will help identify potential new therapeutic targets for CRCaP. We propose to use ChIP-seq, exome-seq and bioinformatics analyses to comprehensively identify AR-regulated genes that drive the growth of human CR-CaP tumors in mice. The longterm aim of this work is to develop a CR-CaP progression gene signature, to identify CR-CaPassociated AR binding site motifs, and to identify potential new therapeutic targets in CRCaP.