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.
Highlights
Many proteins expressed during tumor progression need to be activated by specific proteolysis before exerting their biological role
In order to determine if there is any association between Proprotein convertases (PCs) expression and ovarian tumor progression, we evaluated the expression of the ubiquitously PC’sfurin, PACE-4, PC-7 and PC-5- in normal and cancer ovarian cell lines and primary ovarian tumors showing different survival patterns
In order to determine furin expression in ovarian cancer, we evaluated its mRNA levels in five normal and five cancer cells by RT-PCR
Summary
Many proteins expressed during tumor progression need to be activated by specific proteolysis before exerting their biological role. Growth factors, growth factor receptors and pro-angiogenic proteins are known to be PCs substrates [13,31] This PC family comprises seven members, PC-1/3, PC-2, PC-4, PC-5, PC-7, furin and PACE-4 and the recently identified SKI-1, and NARC-1. 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. 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. Conclusions: Our studies point to a clear relationship between furin and ovarian cancer These results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. Furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease
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