Please use this identifier to cite or link to this item: https://doi.org/10.1007/s10549-007-9516-9
Title: On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer
Authors: Smollich, M.
Götte, M.
Yip, G.W. 
Yong, E.-S.
Kersting, C.
Fischgräbe, J.
Radke, I.
Kiesel, L.
Wülfing, P.
Keywords: Breast cancer
Endothelin
Endothelin-converting enzyme
Neprilysin
RO 67-7447
Issue Date: Dec-2007
Citation: Smollich, M., Götte, M., Yip, G.W., Yong, E.-S., Kersting, C., Fischgräbe, J., Radke, I., Kiesel, L., Wülfing, P. (2007-12). On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer. Breast Cancer Research and Treatment 106 (3) : 361-369. ScholarBank@NUS Repository. https://doi.org/10.1007/s10549-007-9516-9
Abstract: Endothelin-1 (ET-1) and its receptors, ET AR and ET BR, are overexpressed in breast carcinomas. However, little is known about the relevance of endothelin-converting enzyme-1 (ECE-1) and ET-1 degrading neprilysin (NEP). In this study, expression of ECE-1 and NEP was determined in 600 breast cancer tissue samples by immunohistochemistry; staining results were correlated with clinicopathological parameters. For ECE-1 expression, we found a significant correlation with VEGF (P < 0.001) and ET AR expression (P = 0.048). While patients with ECE-1 overexpressing tumours had more frequent disease recurrence (P = 0.03), NEP overexpression correlated with improved disease-free survival (DFS) (P = 0.023) and less frequent metastasis (P = 0.046). Also, a decrease of NEP expression with malignant progression (G1-G3) was found. ECE-1 inhibition using the selective ECE-1 inhibitor RO 67-7447 in MCF-7 breast cancer cells led to a significantly decreased ET-1 expression and reduced cell invasiveness (54.3% of controls, P = 0.014). Our results indicate that overexpression of ECE-1 is associated with unfavourable outcome, whereas NEP positively influences survival. Thus, expression of ECE-1 and NEP may have prognostic relevance. Due to the anti-invasive effect of the selective ECE-1 inhibitor, targeting ECE-1 may represent an innovative option in future breast cancer therapy. © 2007 Springer Science+Business Media, LLC.
Source Title: Breast Cancer Research and Treatment
URI: http://scholarbank.nus.edu.sg/handle/10635/120675
ISSN: 01676806
DOI: 10.1007/s10549-007-9516-9
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