title: The transcriptomics of de novo androgen biosynthesis in prostate cancer cells following androgen reduction.
abstract: The progression of prostate cancer to the castration-recurrent phenotype remains a major problem medically. The present study examined the transcriptomics of de novo androgen synthesis as a potential mechanism to escape from dependence on circulating androgen. VCaP, LNCaP and LAPC4 cells were acclimated to 1 nM testosterone for five generations before subjecting them to a reduced level of 0.03 nM testosterone. Changes in gene expression were quantified using qRT-PCR. Analyses of the cholesterol biosynthesis pathway and the Δ4, Δ5 and backdoor steroidogenic pathways were carried out. VCaP cells showed no change in the transcriptome of cholesterol biosynthesis. However, several receptors for cholesterol transport were upregulated. The Δ4 and Δ5 steroidogenic pathways, but not the backdoor pathway, were stimulated. Additionally, androgen receptor (AR) expression was increased. Taken together, the above changes might allow recovery of AR activity to a near normal level. In contrast, LNCaP cells showed only minimal adjustment in the transcriptome of steroidogenesis. LAPC4 cells were equally unresponsive to boosting the machinery of androgen production. In brief, our results suggest that the VCaP model is an appropriate model for further investigation of targeting the androgen-AR axis to block the emergence of castration-resistant prostate cancer.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Cheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.forename: James L
authors.initials: JL
authors.lastname: Mohler
authors.forename: Clement
authors.initials: C
authors.lastname: Ip
mesh_terms: D000728:Androgens / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics; D013739:Testosterone / Q000096:biosynthesis / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000728:Androgens; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D002784:Cholesterol
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