RNA Editing of Androgen Receptor Gene Transcripts in Prostate Cancer Cells

摘要: Reactivation of the androgen receptor (AR) signaling pathway represents a critical step in growth and survival androgen-independent (AI) prostate cancer (CaP). In this study we show DU145 PC3 AI human CaP cell lines respond to androgens require AR expression for optimal proliferation vitro. Interestingly, gene transcripts cells harbored large number single base pair nucleotide transitions that resulted missense mutations selected codons. The most notable lesion detected included oncogenic codon 877T→A gain-of-function mutation. Surprisingly, transcript were not genome-encoded substitutions, but instead co-localized putative A-to-I, U-to-C, C-to-U, G-to-A RNA editing sites, suggesting lesions mediated through mechanisms. Higher levels mRNA encoding A-to-I enzymes ADAR1 ADARB1 observed relative androgen-responsive LNCaP 22Rv1 lines, which correlated with higher cells. Our results suggest are targeted by different Thus may contribute etiology hormone-refractory phenotypes advanced stage CaP.