Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression

Nat Med. 1998 Jan;4(1):50-7. doi: 10.1038/nm0198-050.


Neutral endopeptidase 24.11 (NEP) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). We report that NEP expression and catalytic activity are lost in vitro in androgen-independent but not androgen-dependent PC cell lines. In vivo, NEP protein expression is commonly decreased in cancer cells of metastatic PC specimens from patients with androgen-independent but not androgen-dependent PC. Overexpression of NEP in androgen-independent PC cells or incubation with recombinant NEP inhibits PC cell growth. Furthermore, in androgen-dependent PC cells, expression of NEP is transcriptionally regulated by androgen and decreases with androgen withdrawal. These data suggest that decreased NEP expression, common in androgen-independent PCs, is facilitated by the elimination of androgens, and that NEP loss plays an important role in the development of androgen-independent PC by allowing PC cells to use mitogenic neuropeptides as an alternate source to androgen in order to stimulate cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biopsy
  • Cell Division / drug effects
  • Cell Nucleus / metabolism
  • Dihydrotestosterone / pharmacology
  • Disease Progression
  • Gene Transfer Techniques
  • Humans
  • Kinetics
  • Male
  • Neoplasm Metastasis
  • Neprilysin / analysis
  • Neprilysin / biosynthesis*
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / pathology*
  • Recombinant Proteins / biosynthesis
  • Tetracycline / pharmacology
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • Recombinant Proteins
  • Dihydrotestosterone
  • Neprilysin
  • Tetracycline