Effect Of Enzalutamide (Ez) Exposure Time On Androgen Receptor (Ar) Splice Variant (Sv) Expression And Gene Transcription Correlates In Androgen-Dependent A) Prostate Cancer (Pc) Cells

e22066 Background: The emergence of castration-resistant (CR) PC limits the benefits of androgen deprivation therapy (ADT) in controlling recurrent AD PC. ARSVs lacking the ligand-binding domain are frequent in CRPC tissue/cells where they mediate resistance to anti-androgens and androgen synthesis inhibitors by regulation of a mitosis-dependent, ARSV-driven transcriptome program (TP) that differs from the differentiation-driving program of full-length (fl) AR. We postulated that ARSVs emerge as a stress reaction to AR suppression and only later induce the TP changes of CRPC. Methods: We assessed the effects of treatment with the anti-androgen EZ (EZt) over 19 culture passages (cp) on AD LNCaP cells (AD-cells), isogenic androgen-independent (AI) cells (AI-cells) and AI CW22RV1 (RV1) cells: growth in androgen-replete or –deprived medium (RM, DM) (MTT assay, cell counts); flAR and ARSV expression (Q-PCR) and the genome-wide TP (Affymetrix Human Exon microarray using 1.3X differential expression and t-tests ...