| Literature DB >> 9427606 |
C N Papandreou1, B Usmani, Y Geng, T Bogenrieder, R Freeman, S Wilk, C L Finstad, V E Reuter, C T Powell, D Scheinberg, C Magill, H I Scher, A P Albino, D M Nanus.
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.Entities:
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Year: 1998 PMID： 9427606 DOI： 10.1038/nm0198-050
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440