title: A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum.
abstract: OBJECTIVE
  Prostate-specific antigen (PSA) is a widely used serum marker for human prostate cancer (PCa). The majority of PSA in serum is present as a complex with alpha-1-antichymotrypsin (ACT). In recent years, the ratio of free (uncomplexed) to total PSA has shown improved discrimination of PCa from benign prostatic hyperplasia. This study examines the nature of the free PSA from detected in PCa serum and shows that some of the uncomplexed PSA is an inactive precursor of PSA (pPSA).
  
  
  METHODS
  Western blot analysis was used to detect clipped, fragment forms of PSA in sera and seminal fluid. Hydrophobic interaction chromatography-high performance liquid chromatography (HIC-HPLC) was used to identify forms of PSA present in the free PSA population. Pooled sera was passed over a PSA immunoaffinity column, and the eluted PSA components were further resolved by HIC-HPLC.
  
  
  RESULTS
  Western blot analysis of whole sera showed complexed PSA and the intact, approximately 34 kilodalton free PSA. Only negligible levels of clipped or degraded forms of PSA, as found in seminal fluid, were detected. Column fractions measured for uncomplexed PSA using the Tandem-MP free PSA assay showed that about 25% of the free PSA eluted as pPSA beginning at the [-4]amino acid. Studies with purified recombinant [-4]pPSA showed that this proenzyme form is inactive and does not complex with ACT.
  
  
  CONCLUSIONS
  These results suggest that the uncomplexed PSA in PCa serum is primarily unclipped PSA that contains a significant fraction of pPSA.
authors.affiliation: Hybritech Incorporated, San Diego, California, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Mikolajczyk
authors.forename: L S
authors.initials: LS
authors.lastname: Grauer
authors.forename: L S
authors.initials: LS
authors.lastname: Millar
authors.forename: T M
authors.initials: TM
authors.lastname: Hill
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: H G
authors.initials: HG
authors.lastname: Rittenhouse
authors.forename: R L
authors.initials: RL
authors.lastname: Wolfert
authors.forename: M S
authors.initials: MS
authors.lastname: Saedi
mesh_terms: D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000302:isolation & purification; D011471:Prostatic Neoplasms / Q000097:blood*; D011498:Protein Precursors / Q000097:blood* / Q000302:isolation & purification
chemical_list: D011498:Protein Precursors; D017430:Prostate-Specific Antigen