Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

V体育官网 - Abstract

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation VSports app下载. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c. c. 0. 469, p=0. 001) and cytoplasmic pARS578 (c. c. 0. 426 p=0. 002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0. 001 and p=0. 036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0. 001) and nucleus (p=0. 038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0. 005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target.