Document Detail


Herpesvirus saimiri-based endothelin-converting enzyme-1 shRNA expression decreases prostate cancer cell invasion and migration.
MedLine Citation:
PMID:  20949559     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The zinc metalloprotease, endothelin-converting enzyme-1 (ECE-1), which converts the mitogenic peptide endothelin-1 (ET-1) from its biologically inactive precursor big-ET-1, is commonly upregulated in prostate cancer (PC) cells. Consequently, we have sought to suppress ECE-1 expression by using RNAi as a potentially novel therapeutic approach. Therefore, a synthetic 64-nt short-hairpin RNA (shRNA), designed to target the ECE-1 gene, was expressed in an Herpesvirus saimiri (HVS)-based delivery vector. ECE-1 expression in cells transduced with the vector was examined by real-time PCR and Western blotting. The effects of ECE-1 knockdown on PC cell migration and invasion were studied using a scratch assay and Matrigel invasion. These studies, in vitro and ex vivo, demonstrated that the HVS-shRNA viruses could infect and silence ECE-1 expression effectively in human PC cells. Furthermore, it was observed that ECE-1 knockdown in either stromal cells or epithelial cells could significantly reduce invasion of PC-3 cells in coculture by 33 and 31%, respectively. In addition, suppressed migration was also observed in HVS-ECE-1 shRNA-infected PC-3 cells compared to uninfected and HVS-GFP-infected control cell cultures. These findings highlight the potential tumor-suppressing effect of ECE-1 knockdown in cancer cells and novel strategies for future therapeutic developments in advanced PC.
Authors:
Yue Hong; Stuart Macnab; Louise A Lambert; Anthony J Turner; Adrian Whitehouse; Badar A Usmani
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Publication Detail:
Type:  Journal Article     Date:  2010-12-02
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  129     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-05-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  586-98     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 UICC.
Affiliation:
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
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