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UBC Theses and Dissertations

Gene expression in prostate cancer Romanuik, Tammy Lee

Abstract

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 (L0ngSAGE) libraries. We identified 35 genes with novel associations to androgen signalling and validated 24 of these genes using quantitative real time-polymerase chain reaction (qRT-PCR). These genes were: ARL6IF5, BL VRB, C]9orf48, C]orfJ22, C6orf66, CAMK2NJ, CCNI, DERA, ERRFI], GLUL, GOLFH3, HMJ3, HSP9OB], MANEA, NANS, NIPSNAP3A, SLC4JA], SOD], SVIF, TAOK3, TCP], TMEM66, USP33, and VTAJ. The physiological relevance of these expression trends was evaluated in vivo using the LNCaP Hollow Fibre model. There is no cure for castration-recurrent prostate cancer (CRPC), and the mechanisms underlying the disease are not known. To address this problem, we assayed the transcriptome of LNCaP human prostate cancer cells as they progress to castration-recurrence in vivo using replicate L0ngSAGE libraries. We identified 96 novel genes consistently differentially expressed in CRPC. The expression profiles support a role for the transcriptional activity of the androgen receptor genes (CCNH, CUEDC2, FLNA, and FSMA 7), steroid synthesis and metabolism genes (DHCR24, DHRS7, ELOVL5, HSDJ 7B4, and OPRKJ), neuroendocrine cell genes (ENO2, MAOA, OPRK], SJOOA]O, and TRPM8), and proliferation genes (GAS5, GNB2L], MT-ND3, NKX3-], PCGEM], PTGFR, STEAFJ, and TMEM3OA) in castration-recurrence. Screening for prostate cancer using serum levels of prostate-specific antigen has resulted in the over-treatment of indolent disease. Novel diagnostic and prognostic markers for prostate cancer are required. To address this need, the levels of 27 transcripts were investigated with qRT-PCR. Expression of POP3 (100 kb from EST CF140309) was prostate-specific, with restricted expression ofADAM2, POP1 (50 kb from AK000023), POP4 (truncated TMEFF2), POP 10 (intron ofADAM2), ELOVL5, RAMP], and SPON2. ELO VL5, NGFRAP1, POP5 (intron of NCAM2), POP8 (intron of EFNA5), RAMP], SPON2, and TMEM66 were differentially expressed between laser microdissected tumour and normal clinical samples of prostatic tissue. These studies suggest that ADAM2, ELOVL5, POP 1, POP3, POP4, POP 10, RAMP], and SPON2 may be good candidates for biomarkers of prostate cancer.

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