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BioMed Research International
Volume 2015, Article ID 148651, 8 pages
http://dx.doi.org/10.1155/2015/148651
Research Article

Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth

1Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
2Laboratory of Biochemical Neuroendocrinology, Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada H2W 1R7
3Angiogenesis Laboratory, Université Bordeaux I, 33400 Talence, France
4INSERM, UMR 1029, 33400 Talence, France

Received 11 September 2014; Revised 30 December 2014; Accepted 11 January 2015

Academic Editor: Athanasios G. Pallis

Copyright © 2015 Jeroen Declercq et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Proprotein convertases are subtilisin-like serine endoproteases that cleave and hence activate a variety of proproteins, including growth factors, receptors, metalloproteases, and extracellular matrix proteins. Therefore, it has been suggested that inhibition of the ubiquitously expressed proprotein convertase FURIN might be a good therapeutic strategy for several tumor types. Whether this is also the case for hepatocellular carcinoma (HCC) is currently not clear. In a mouse model for HCC expression of Furin was not altered in the tumors, while those of PC7, PC5/6, and PACE4 significantly decreased, at least at some time points. To investigate the impact of Furin inhibition on the development and progression of HCC in this model, Furin was genetically ablated in the liver. Furin inactivation resulted in an increased tumor mass after 5 weeks. This was not caused by decreased apoptosis, since no differences in the apoptosis index could be observed. However, it could at least partially be explained by increased hepatocyte proliferation at 5 weeks. The tumors of the Furin knockout mice were histologically similar to those in wild type mice. In conclusion, liver-specific Furin inhibition in HCC enhances the tumor formation and will not be a good therapeutic strategy for this tumor type.