Identification of novel androgen-responsive genes by sequencing of LongSAGE libraries.
BACKGROUND
The 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.


RESULTS
There were 131 tags (87 genes) that displayed statistically significant (p <or= 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.


CONCLUSIONS
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.
Romanuik
Tammy L
TL
Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. tromanuik@cw.bc.ca
Wang
Gang
G
Holt
Robert A
RA
Jones
Steven J M
SJ
Marra
Marco A
MA
Sadar
Marianne D
MD
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics
D000728:Androgens; D012334:RNA, Neoplasm