Project description:Transriptome analysis of VCAP and CWR22-Pc cell lines after concomittant treatment with androgen with bicalutamide and enzalutamide
Project description:Transriptome analysis of prostate tumors from Hi-Myc mouse prostates 3 days after castration or treatment with bicalutamide or enzalutamide
Project description:The goal of this analysis is to profile AR-regulated genes, especially non-coding RNAs in three androgen sensitive prostate cancer cell lines, MDA-PCA-2B, LNCaP and VCaP. The two cell lines were serum-starved first, followed by dihydrotestosterone (DHT) stimulation or treated with Enzalutamide (AR inhibitor) without starvation. Transcriptome profiling was generated by RNA-sequencing from polyA-selected RNA. These experiments are followed by knock-down experiments of AR and ARlnc1 in MDA-PCA-2B, and also Enzalutamide (anti-androgen) treatment of LNCaP cells.
Project description:Gene expression in LNCaP cells after treatment with the androgen receptor targeting drugs bicalutamide (BIC), enzalutamide (ENZ) and apalutamide (ARN) in the presence or absence of dihydrotestosterone (DHT).
Project description:We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate (CPA), mifepristone (RU486) and bicalutamide (Bica) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies.
Project description:We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate (CPA), mifepristone (RU486) and bicalutamide (Bica) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies. Examination of AR and GR binding sites in LNCaP-1F5 and VCaP cells in presence of DHT and Dex respectively. Further analysis of AR binding sites in LNCaP-1F5 cells treated with partial agonist/antagonists, CPA, RU486 and Bica. Additionally RNA Pol II mapping is performed in cells treated with DHT and Dex.
Project description:Prostate cancer patients benefit from treatment with androgen receptor signaling inhibitors such as AR antagonists. The emergence of resistance to the clinically applied AR antagonists opens up the need for development of alternative AR antagonists. We show here the development of a novel AR antagonists that is structurally different from enzalutamide. Moreover, MEL-6 remains active in the presence of several AR mutations (T877A, W741C and F876L) that are found in patients resistant to hydroxyflutamide, bicalutamide and enzalutamide. To validate the androgen receptor (AR) as the target of our experimental AR antagonist, MEL-6, we investigated the effect of MEL-6 treatment on the prostate cancer cell line, LNCaP.
