Abstract 174: MicroRNA signatures of castration resistant human prostate cancer

Abstract

Abstract Androgen-dependent (AD) prostate cancer (CaP) typically progresses to castration resistant prostate cancer (CRPC) after after some duration of androgen deprivation therapy (ADT). The mechanisms of this transition are at the beginning to be understood. MicroRNAs (miRs) are non-coding small RNAs (19-25nt) that play an important role in the regulation of gene expression. So far, only a few studies have looked at prostate cancer-specific miRNA signatures relevant to the development and progression of CaP. By performing genome-wide expression profiling of miRs, we found 7 miRs (miR-221, miR-222, miR-15a, miR-16-1, miR-203, miR-23b and miR-27b) differentially expressed in the AD prostate cancer LNCaP cell line and the LNCaP derived CRPC cell line- LNCaP-Abl. In particular miR-221 and miR-222, were most dramatically increased in the CRPC cell lines. Over-expression of miR-221 or -222 in LNCaP or another AD cell line, LAPC-4 significantly reduced the level of the dihydrotestosterone (DHT) induced up-regulation of PSA expression and increased androgen independent (AI) growth of LNCaP cells. Knocking down the expression level of miR-221 and -222 with antagonist miRs in the LNCaP-Abl cell line restored the response to DHT induction of PSA transcription and also increased the growth response of LNCaP-Abl cells to androgen. To determine the clinical relevance of the differential expression patterns of these miRs, we compared the expression levels of these 7 miRs in 86 normal prostate tissues, 34 localized hormone naïve primary tumors and 17 bone metastatic CRPC samples. Despite of the anticipated heterogeneity of CRPCs within each individual or among patients, surprisingly ∼90% of analyzed CRPC tumors can be characterized by significant up-regulation of miR-221/-222 and down-regulation of miR-23b/-27b. This finding suggests that the signature of altered miR-221/-222 and miR-23b/-27b expression is associated with the development of CRPC in human tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 174. doi:10.1158/1538-7445.AM2011-174