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Cellular Oncology
Volume 29 (2007), Issue 4, Pages 289-299
http://dx.doi.org/10.1155/2007/930321

Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer

Robert E. Page,1 Andrés J. P. Klein-Szanto,1,5 Samuel Litwin,2 Emmanuelle Nicolas,3 Raid Al-Jumaily,1 Peter Alexander,1 Andrew K. Godwin,4 Eric A. Ross,2 Russell J. Schilder,4 and Daniel E. Bassi1,4,5

1Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
2Department of Biomathematics and Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
3Department of Basic Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
4Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
5Tumor Cell Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

Copyright © 2007 Hindawi Publishing Corporation and the authors. 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

Background: Proprotein convertases (PCs) are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and angiogenic factors. Although the expression of several PCs is increased in many tumors, their expression in primary ovarian tumors has not been studied in detail. We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression. Methods: We assessed their expression by RT-PCR, Real-time PCR, Western blot, and immunohistochemistry using cells derived from normal human ovarian surface epithelium (HOSE) and cancer cell lines as well as ovarian epithelial cancer specimens (45 RT-PCR/Real-time PCR, and 120 archival specimens for Immunohistochemistry). Results: We found that furin expression was restricted to the cancer cell lines. In contrast, PACE-4 and PC-7 showed expression only in normal HOSE cells lines. Furthermore, furin was predominantly expressed in primary tumors from patients who survived for less than five years. The other PCs are either expressed in the group of survivors (PC-7 and PACE4) or expressed in low amounts (PC-5). Conclusions: Our studies point to a clear relationship between furin and ovarian cancer. In addition, these results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. In summary, furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease.