Mapping of DHT-responsive or -independent AR-binding sites induced by activated Src in prostate cancer cell lines [RNA-seq]

Building on the observation that metastatic, castration-resistant prostate cancer (CRPC) correlates with activation of Src-family tyrosine kinases, we showed that the expression of activated Src renders LNCaP androgen-independent. Here, we report on RNA-seq and/or AR ChIP-seq analyses of LNCaP, LNCaP[Src], VCaP, 22Rv1 cells grown in the presence or absence of 10 nM DHT for 16h, or LuCaP35.1 tumors grown in androgen-supplemented vs. castrated mice (androgen-dependent vs. castration-resistant). We identify an 11-gene Src-induced signature found only in CRPC in response to DHT, and moreover, the differentail expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival. Overall design: RNA-seq of NGS libraries and sequencing of prostate cancer cell lines. 16 samples are seqeunced. For VCaP, LnCap, LnCap-SRC, 22RV1, and LNCap-C4-2, we have both DHT treated and control cell lines. For LuCaP 35.1 cell line, xenografted scid mice tumors are seqeucned, 3 androgen-dependent and 3 castration-recurrent samples ar sequenced.