title: Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients.
abstract: OBJECTIVE
  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. 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.
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.|Academic Department of Surgery, School of Medicine, University of Glasgow, Walton Building, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Patek
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.|Academic Department of Surgery, School of Medicine, University of Glasgow, Walton Building, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Willder
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: Heng
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Taylor
authors.affiliation: Academic Department of Surgery, School of Medicine, University of Glasgow, Walton Building, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Horgan
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.|Beatson Institute of Cancer Research, Glasgow G61 1BD, UK.|Department of Urology, Queen Elizabeth University Hospital, Glasgow G31 2ER, UK.
authors.forename: Hing
authors.initials: H
authors.lastname: Leung
authors.affiliation: Department of Urology, Queen Elizabeth University Hospital, Glasgow G31 2ER, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Underwood
authors.affiliation: Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Edwards
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D012694:Serine; D011493:Protein Kinase C
keywords: androgen receptor; biomarker; phosphorylation; prostate cancer; protein kinase C