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

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

*Corresponding author for this work
55 Citations (Scopus)


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.

Original languageEnglish
JournalBreast Cancer Research and Treatment
Issue number3
Pages (from-to)361-369
Number of pages9
Publication statusPublished - 12.2007

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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