High Expression of PSM-E Correlated With Tumor Grade in Prostate Cancer: A New Alternatively Spliced Variant of Prostate-Specific Membrane Antigen

Prostate. 2007 Dec 1;67(16):1791-800. doi: 10.1002/pros.20664.

Abstract

Background: Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer (PCa) has been targeted for therapy and diagnosis of PCa. In the current study, PSMA cDNA was cloned from PCa tissue by RT-PCR. After sequencing, a new spliced variant of PSMA (PSM-E) was discovered and its specificity in PCa was evaluated.

Methods: PSM-E and PSMA mRNA were measured in LNCaP, PC-3 and prostate or nonprostatic malignancies. Following transfection of PC-3 with PSM-E cDNA in the pcDNA3.0 vector, PSM-E expression was measured by immunofluorescence and Western-blot. PSM-E and PSMA mRNA levels were quantified by a real-time PCR assay in normal prostate (n = 7), benign prostatic hyperplasia (BPH) (n = 22) and PCa (n = 41). The correlation between their levels and tumor grade was analyzed.

Results: PSM-E cDNA is identical to PSMA except for a 97-nucleotide region and a 93-nucleotide region. PSM-E and PSMA mRNA were detected in PCa and LNCaP, not in PC-3; PSMA could be detected in some nonprostatic tumors whereas PSM-E not. The expression of PSM-E protein was detected in transfected cells. Significant difference of PSM-E mRNA levels was observed among normal prostate, BPH and PCa (P < 0.001), and PSM-E levels increased with increasing Gleason score (r = 0.514, P < 0.001). PSMA mRNA levels were higher in BPH and PCa than in normal prostate (P < 0.001), but no difference between BPH and PCa, no significant correlation was observed between PSMA levels and Gleason score (r = 0.229, P = 0.057).

Conclusions: PSM-E may be a potential prognostic indicator for PCa progression and may be a new target antigen for therapy of PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Antigens, Surface / biosynthesis*
  • Antigens, Surface / genetics
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • Cloning, Molecular
  • Glutamate Carboxypeptidase II / biosynthesis*
  • Glutamate Carboxypeptidase II / genetics
  • Humans
  • Male
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Protein Isoforms
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Statistics, Nonparametric
  • Transfection

Substances

  • Antigens, Surface
  • Protein Isoforms
  • RNA, Messenger
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II