Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression Academic Article Article uri icon

Overview

MeSH Major

  • Antineoplastic Agents
  • Molecular Diagnostic Techniques
  • Molecular Targeted Therapy
  • Neoplasms

abstract

  • 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 date

  • April 4, 1998

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1038/nm0198-050

PubMed ID

  • 9427606

Additional Document Info

start page

  • 50

end page

  • 7

volume

  • 4

number

  • 1