Abstract
BackgroundThe development and maintenance of the prostate is dependent on androgens and the androgen receptor. The androgen pathway continues to be important in prostate cancer. Here, we evaluated the transcriptome of prostate cancer cells in response to androgen using long serial analysis of gene expression (LongSAGE) libraries.ResultsThere 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.ConclusionThese 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.
Highlights
The development and maintenance of the prostate is dependent on androgens and the androgen receptor
Androgens mediate their effect through the androgen receptor (AR) and together they play integral roles in the development and maintenance of the prostate
LNCaP human prostate cancer cells were chosen as the model cell line for evaluating androgen signaling because they respond to androgens, express a functional mutated (T877A) AR, they can be grown in vitro as a monolayer or in vivo as a xenograft or in the Hollow Fiber model [27,28,29]
Summary
The development and maintenance of the prostate is dependent on androgens and the androgen receptor. We evaluated the transcriptome of prostate cancer cells in response to androgen using long serial analysis of gene expression (LongSAGE) libraries. 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]. Men that have used excess androgens in the form of anabolic steroids have a higher incidence of prostate cancer [3,4,5]. Association of prostate cancer with levels of androgens (page number not for citation purposes)
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