Neutral Endopeptidase Inhibits Neuropeptide Mediated Growth of Androgen-Independent Prostate Cancer
Abstract
The objective of this project is to elucidate the involvement of neutral endopeptidase (NEP), a cell-surface peptidase which inactivates active peptides and reduces local concentrations of peptide available for receptor binding and signal transduction, in the growth inhibition of androgen-independent (Al) prostate cancer. During the first year of the fellowship, we have for the first time shown that overexpression of cell-surface NEP induces growth inhibition and apoptosis in Al-prostate cancer. This growth inhibition induced by NEP results from PC cells arresting in a Gi phase arrest of the cell cycle and leading to increased expression of p21 and dephosphorylated Rb protein. Induction of NEP can inhibit the tumorigenicity by using the orthotopic model of prostate cancer in which PC cells are directly injected into the prostate. NEP is also involved in integrin mediated signaling pathways. Recombinant NEP and induced NEP can inhibit the bombesin and endothelin-l stimulated FAK phosphorylation and cell migration. These studies will help delineate biological significance of Ni%P loss in the development and maintenance of androgen-independent prostate cancer, and indicate the potential for recombinant NEP or NEP directed gene therapy as therapy in patients Al PC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA388155
Entities
People
- Jie Dai
Organizations
- Weill Cornell Medicine