Project description:Although AR-V7 has been intensively studied, it remains unclear whether AR-V7 can specifically activate a distinctive transcriptional program from the full-length AR (AR-FL), and whether AR-V7 may play a role in accelerating the metastatic progression of castration-resistant PCa (CRPC). In this study, we hypothesize that AR-V7 can drive a distinct transcription program from AR-FL in CRPC condition. To test this, we used LNCaP model with inducible overexpression of AR-V7 or AR-FL to examine the effects of AR-V7 overexpression or AR-FL overexpression stimulated with DHT for 4 hours on AR-V7 or AR-FL cistromes. We also studied the effects of AR-V7 on cistromes of pioneer factor FOXA1 and active histone marker H3K27ac, and the function of phosphorylation at Ser81 on AR-V7 function in CRPC.
Project description:Although AR-V7 has been intensively studied, it remains unclear whether AR-V7 and other AR splicing variants can specifically activate a distinctive transcriptional program from the full-length AR (AR-FL), and whether AR-V7 may play a role in accelerating the metastatic progression of castration-resistant PCa (CRPC). In this study, we hypothesize that AR-V7 can drive a distinct transcription program from AR-FL in CRPC condition. To test this, we performed ATAC-seq using LNCaP model with inducible overexpression of AR-V7 to examine the function of AR-V7. We demonstrated that AR-V7 has “pioneer factor-like” activities to access the androgen-responsive elements (AREs) located at compact chromatin regions. More importantly, we found that SOX9, a critical metastasis driver gene, was a direct target and downstream effector of AR-V7, and its protein expression was dramatically upregulated at AR-V7-induced bone lesions.
