title: PSMA-PSA clones controlled by full Akt phosphorylation (T308+,S473+) recapitulate molecular features of human prostate cancer.
abstract: BACKGROUND
  (PSMA+,PSA+) and (PSMA+,PSA-) are the two most individual clones that we have previously identified during prostate cancer (PC) progression. However, molecular signatures associated with these distinct PSMA-PSA prostate clones and their specific correlation with disease outcome is yet to be defined.
  
  
  OBJECTIVE
  Since Akt is a major pathway involved in the critical activating events that leads to malignant form of the disease, we studied the involvement of full Akt activation (T308+,S473+) connected with serum PSA levels, tissue PSMA expression and angiogenic activity on the emergence of (PSMA+,PSA+) and (PSMA+,PSA-) PC clones.
  
  
  METHODS
  The study was carried out in 6 normal prostate, 25 benign prostate hyperplasia (BPH) and 23 (PC). Immunohistochemical analysis was performed to study the expression of PSMA, PSA, pAkt(T308), pAkt(S473) and CD34 in prostate tissues. The evaluation of angiogenesis was made by CD34 immune marker. Serum levels of PSA were assayed by Immulite autoanalyser.
  
  
  RESULTS
  The most relevant result showed that, among PC patients with pAkt (T308+,S473+) profile, patients that exhibit the (PSMA+,PSA+) clone have .higher serum PSA levels, tissue PSMA expression and angiogenic activity than those with (PSMA+,PSA-) clone. Although have the same (PSMA+,PSA+) prostate clone, BPH patients have distinct molecular-biological features compared to PC patients among pAkt (T308+,S473+) profile. In fact, among patients with maximal Akt activation, the (PSMA+,PSA+) PC clone is characterized by higher serum PSA levels, tissue PSMA production and intensive angiogenic activity than (PSMA+,PSA+) BPH clone.
  
  
  CONCLUSIONS
  These findings emphasize the potential role of the full Akt activation (T308+,S473+) in expansion of several PSMA-PSA prostate clones capable of driving both human PC initiation as well as progression to a metastatic phenotype. Pinpoint patients according to PSMA-PSA clones could recapitulate the histological and molecular features of human PC and may offer a novel approach for controlling metastasis.
authors.forename: Awatef
authors.initials: A
authors.lastname: Ben Jemaa
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouraoui
authors.forename: Sataa
authors.initials: S
authors.lastname: Sallami
authors.forename: Ahmed
authors.initials: A
authors.lastname: Banasr
authors.forename: Yassine
authors.initials: Y
authors.lastname: Nouira
authors.forename: Ali
authors.initials: A
authors.lastname: Horchani
authors.forename: Ridha
authors.initials: R
authors.lastname: Oueslati
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000235:genetics*; D003001:Cloning, Molecular; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D051057:Proto-Oncogene Proteins c-akt; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen