title: Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression.
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.
authors.affiliation: Genitourinary Oncology Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: B
authors.initials: B
authors.lastname: Usmani
authors.forename: Y
authors.initials: Y
authors.lastname: Geng
authors.forename: T
authors.initials: T
authors.lastname: Bogenrieder
authors.forename: R
authors.initials: R
authors.lastname: Freeman
authors.forename: S
authors.initials: S
authors.lastname: Wilk
authors.forename: C L
authors.initials: CL
authors.lastname: Finstad
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
authors.forename: C T
authors.initials: CT
authors.lastname: Powell
authors.forename: D
authors.initials: D
authors.lastname: Scheinberg
authors.forename: C
authors.initials: C
authors.lastname: Magill
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.forename: A P
authors.initials: AP
authors.lastname: Albino
authors.forename: D M
authors.initials: DM
authors.lastname: Nanus
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D018450:Disease Progression; D018014:Gene Transfer Techniques; D006801:Humans; D007700:Kinetics; D008297:Male; D009362:Neoplasm Metastasis; D015260:Neprilysin / Q000032:analysis / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; D013196:Dihydrotestosterone; D015260:Neprilysin; D013752:Tetracycline