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

  


Authors: Papandreou, C. N.; Usmani, B.; Geng, Y.; Bogenrieder, T.; Freeman, R.; Wilk, S.; Finstad, C. L.; Reuter, V. E.; Powell, C. T.; Scheinberg, D.; Magill, C.; Scher, H. I.; Albino, A. P.; Nanus, D. M.
Article 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.
Keywords: human cell; polymerase chain reaction; cell division; protein degradation; tumor markers, biological; tumor cells, cultured; enzyme activity; transfection; biopsy; time factors; carcinogenesis; prostate cancer; prostatic neoplasms; kinetics; disease progression; recombinant proteins; neoplasm metastasis; metastasis potential; cell nucleus; tetracycline; enzyme deficiency; gene transfer techniques; dihydrotestosterone; neprilysin; humans; human; male; priority journal; article; membrane metalloendopeptidase
Journal Title: Nature Medicine
Volume: 4
Issue: 1
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 1998-01-01
Start Page: 50
End Page: 57
Language: English
DOI: 10.1038/nm0198-050
PUBMED: 9427606
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031889217&doi=10.1038%2fnm0198-050&partnerID=40&md5=4c616d3bb39ac7e6360960b7cb5fddec
Notes: Source: Scopus
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MSK Authors
  1. David Scheinberg
    499 Scheinberg
  2. Victor Reuter
    1228 Reuter
  3. Howard Scher
    1130 Scher
  4. C Thomas Powell
    36 Powell
  5. Christos N Papandreou
    20 Papandreou
  6. Yiping Geng
    5 Geng
  7. David M. Nanus
    66 Nanus
  8. Connie L. Finstad
    45 Finstad
  9. Thomas Bogenrieder
    18 Bogenrieder
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