Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth

A. Horiguchi, R. Zheng, O. B. Goodman, R. Shen, H. Guan, L. B. Hersh, D. M. Nanus

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Neprilysin (neutral endopeptidase, NEP) is a cell surface peptidase whose expression is lost in approximately 50% of prostate cancers (PC). NEP normally functions to inactivate peptides such as bombesin and endothelin-1, and potentiates the effects of the PTEN tumor suppressor via a direct protein-protein interaction. NEP loss contributes to PC progression. We investigated the therapeutic efficacy of using a lentiviral vector system to restore NEP expression in PC cells. Third-generation lentiviral vectors encoding wild-type NEP (L-NEP) or green fluorescent protein (L-GFP) were introduced into NEP-deficient 22RV1 PC cells. Cells infected with L-NEP or L-GFP at a multiplicity of infection of 10 demonstrated NEP enzyme activity of 1171.2±4.9 and 17.2±5.3 pmol/μg/min (P<0.0001), respectively. Cell viability, proliferation and invasion were each significantly inhibited in 22RV1 cells expressing NEP compared with control cells infected with L-GFP (P<0.01). Analysis of known downstream effects of NEP showed NEP-expressing cells exhibiting decreased Akt and focal adhesion kinase phosphorylation and increased PTEN protein expression. Finally, injection of L-NEP into established 22RV1 xenograft tumors significantly inhibited tumor growth (P<0.01). These experiments demonstrate that lentiviral NEP gene transfer is a novel targeted strategy for the treatment of NEP-deficient PC.

Original languageEnglish
Pages (from-to)583-589
Number of pages7
JournalCancer Gene Therapy
Issue number6
StatePublished - Jun 2007

Bibliographical note

Funding Information:
This work was supported by NIH Grants CA80240(DMN), DA02243 (LBH), NCRR P20RR020171 (LBH) and DOD PC040758 (DMN), and the Robert H McCooey Memorial Cancer Research Fund (DMN).


  • Lentivirus
  • Neprilysin
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research


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