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

Christos N. Papandreou, Badar Usmani, Yiping Geng, Thomas Bogenrieder, Ronald Freeman, Sherwin Wilk, Connie L. Finstad, Victor E. Reuter, C. Thomas Powell, David Scheinberg, Catherine Magill, Howard L. Scher, Anthony P. Albino, David M. Nanus

Research output: Contribution to journalArticlepeer-review

247 Scopus citations

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.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalNature Medicine
Volume4
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

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