Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells.
Proteins responsive to androgen and anti-androgen may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-ablation therapy. These proteins represent potential diagnostic and therapeutic targets for improved management of prostate cancer. We have investigated the effect of androgen (R1881) and anti-androgen (bicalutamide) on the androgen-responsive prostate cancer LNCaP cell line using a quantitative gel-based proteomic approach. Prior to analysis, the in vitro system was evaluated for reproducibility and validated by appropriate molecular responses to treatment. Six replicate samples were independently generated and analysed by 2-D DIGE. According to strict statistical criteria, 197 spots were differentially expressed, of which we have successfully identified 165 spots corresponding to 125 distinct proteins. Following androgen supplementation, 108 spots (68 proteins) were increased and 57 spots (39 proteins) were decreased. Essentially no difference was observed between control and anti-androgen-treated samples, confirming the absence of "off-target" effects of bicalutamide. Identified proteins were involved in diverse processes including the stress response and intracellular signalling. The potential contribution to disease of these processes and identified constituent proteins are discussed. This rigorous, statistically supported study of androgen responses has provided a number of potential candidates for development as diagnostic/prognostic markers and drug targets.
Rowland
John G
JG
Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne, UK.
Robson
Joanne L
JL
Simon
William J
WJ
Leung
Hing Y
HY
Slabas
Antoni R
AR
D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D000813:Anilides / Q000494:pharmacology; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014105:Tosyl Compounds
D000728:Androgens; D000813:Anilides; D009570:Nitriles; D020543:Proteome; D014105:Tosyl Compounds; D015741:Metribolone; C053541:bicalutamide