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

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 sev...

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Main Authors: Robert E. Page, Andrés J. P. Klein-Szanto, Samuel Litwin, Emmanuelle Nicolas, Raid Al-Jumaily, Peter Alexander, Andrew K. Godwin, Eric A. Ross, Russell J. Schilder, Daniel E. Bassi
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.1155/2007/930321
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author Robert E. Page
Andrés J. P. Klein-Szanto
Samuel Litwin
Emmanuelle Nicolas
Raid Al-Jumaily
Peter Alexander
Andrew K. Godwin
Eric A. Ross
Russell J. Schilder
Daniel E. Bassi
author_facet Robert E. Page
Andrés J. P. Klein-Szanto
Samuel Litwin
Emmanuelle Nicolas
Raid Al-Jumaily
Peter Alexander
Andrew K. Godwin
Eric A. Ross
Russell J. Schilder
Daniel E. Bassi
author_sort Robert E. Page
collection DOAJ
description 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.
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spelling doaj-art-9faf7f9114374427b3d720237c5d8ca02025-02-03T00:59:31ZengWileyCellular Oncology1570-58701875-86062007-01-0129428929910.1155/2007/930321Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian CancerRobert E. Page0Andrés J. P. Klein-Szanto1Samuel Litwin2Emmanuelle Nicolas3Raid Al-Jumaily4Peter Alexander5Andrew K. Godwin6Eric A. Ross7Russell J. Schilder8Daniel E. Bassi9Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Biomathematics and Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Basic Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USAOvarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Biomathematics and Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USAOvarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USADepartment of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USABackground: 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.http://dx.doi.org/10.1155/2007/930321
spellingShingle Robert E. Page
Andrés J. P. Klein-Szanto
Samuel Litwin
Emmanuelle Nicolas
Raid Al-Jumaily
Peter Alexander
Andrew K. Godwin
Eric A. Ross
Russell J. Schilder
Daniel E. Bassi
Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer
Cellular Oncology
title Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer
title_full Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer
title_fullStr Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer
title_full_unstemmed Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer
title_short Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer
title_sort increased expression of the pro protein convertase furin predicts decreased survival in ovarian cancer
url http://dx.doi.org/10.1155/2007/930321
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