Quantitative proteomic determination of diethylstilbestrol action on prostate cancer

Abstract : Diethylstilbestrol (DES) has a direct cellular mechanism inhibition on prostate cancer. Its action is independent from the oestrogen receptors and is preserved after a first-line hormonal therapy. We aimed to identify proteins involved in the direct cellular inhibition effects of DES on prostate cancer. We used a clonogenic assay to establish the median lethal concentration of DES on 22RV1 cells. 22RV1 cells were exposed to standard and DES-enriched medium. After extraction, protein expression levels were obtained by two-dimensional differential in-gel electrophoresis (2D-DIGE) and isotope labelling tags for relative and absolute quantification (iTRAQ). Proteins of interest were analysed by quantitative RT-PCR and western blotting. The differentially regulated proteins (P$<$0.01) were interrogated against a global molecular network based on the ingenuity knowledge base. The 2D-DIGE analyses revealed DES-induced expression changes for 14 proteins ($>$1.3 fold; P$<$0.05). The iTRAQ analyses allowed the identification of 895 proteins. Among these proteins, 65 had a modified expression due to DES exposure (i.e., 23 overexpressed and 42 underexpressed). Most of these proteins were implicated in apoptosis and redox processes and had a predicted mitochondrial expression. Additionally, ingenuity pathway analysis placed the OAT and HSBP1 genes at the centre of a highly significant network. RT-PCR confirmed the overexpression of OAT (P50.006) and HSPB1 (P50.046).
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Asian Journal of Andrology, Medknow Publications, 2013, 15, pp.413-420. 〈10.1038/aja.2012.128〉
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Pierre Bigot, Kevin Mouzat, Souhil Lebdai, Muriel Bahut, Nora Benhabiles, et al.. Quantitative proteomic determination of diethylstilbestrol action on prostate cancer. Asian Journal of Andrology, Medknow Publications, 2013, 15, pp.413-420. 〈10.1038/aja.2012.128〉. 〈hal-01543057〉

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