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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2007

01-12-2007 | Preclinical Study

On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer

Authors: Martin Smollich, Martin Götte, George W. Yip, Eng-Siang Yong, Christian Kersting, Jeanett Fischgräbe, Isabel Radke, Ludwig Kiesel, Pia Wülfing

Published in: Breast Cancer Research and Treatment | Issue 3/2007

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Abstract

Endothelin-1 (ET-1) and its receptors, ETAR and ETBR, 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 ETAR 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.
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Metadata
Title
On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer
Authors
Martin Smollich
Martin Götte
George W. Yip
Eng-Siang Yong
Christian Kersting
Jeanett Fischgräbe
Isabel Radke
Ludwig Kiesel
Pia Wülfing
Publication date
01-12-2007
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2007
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9516-9

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