TY - JOUR
T1 - On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer
AU - Smollich, Martin
AU - Götte, Martin
AU - Yip, George W.
AU - Yong, Eng Siang
AU - Kersting, Christian
AU - Fischgräbe, Jeanett
AU - Radke, Isabel
AU - Kiesel, Ludwig
AU - Wülfing, Pia
N1 - Funding Information:
Acknowledgements We thank Barbara Kloke and Birgit Pers for excellent technical assistance. Funding was provided by Münster University Hospital ‘‘Innovative Medizinische Fors-chung’’ IMF grants WÜ 120332 and WÜ 110527. Work in G.W.Y.’s lab is supported by Grants NMRC/0772/2003 and NMRC/1023/2005 from the National Medical Research Council, Singapore.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=35649009395&partnerID=8YFLogxK
U2 - 10.1007/s10549-007-9516-9
DO - 10.1007/s10549-007-9516-9
M3 - Journal articles
C2 - 17295044
AN - SCOPUS:35649009395
SN - 0167-6806
VL - 106
SP - 361
EP - 369
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -
