Identification of novel androgen-responsive genes by sequencing of LongSAGE libraries

There were 131 tags (87 genes) that displayed statistically significant (p ≤ 0.001) differences in expression in response to androgen. Many of the genes identified by LongSAGE (35/87) have not been previously reported to change expression in the direction or sense observed. In regulatory regions of the promoter and/or enhancer regions of some of these genes there are confirmed or potential androgen response elements (AREs). The expression trends of 24 novel genes were validated using quantitative real time-polymerase chain reaction (qRT-PCR). These genes were: ARL6IP5, BLVRB, C19orf48, C1orf122, C6orf66, CAMK2N1, CCNI, DERA, ERRFI1, GLUL, GOLPH3, HM13, HSP90B1, MANEA, NANS, NIPSNAP3A, SLC41A1, SOD1, SVIP, TAOK3, TCP1, TMEM66, USP33, and VTA1. The physiological relevance of these expression trends was evaluated in vivo using the LNCaP Hollow Fibre model. Novel androgen-responsive genes identified here participate in protein synthesis and trafficking, response to oxidative stress, transcription, proliferation, apoptosis, and differentiation.These processes may represent the molecular mechanisms of androgen-dependency of the prostate. Genes that participate in these pathways may be targets for therapies or biomarkers of prostate cancer.Androgens mediate their effect through the androgen receptor (AR) and together they play integral roles in the development and maintenance of the prostate. In the absence of a functional androgen-axis during development, the prostate will fail to form[1]. The size of the prostate increases with the elevation of levels of androgens in males during puberty[2]. Androgens promote proliferation, differentiation, and survival of prostate cells[1]. Men that have used excess androgens in the form of anabolic steroids have a higher incidence of prostate cancer [3-5]. Association of prostate cancer with levels of androgens has also been reported in rodents[6,7]. Reduction of androgen in humans or dogs before puberty by castration is associated wit