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 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.
Page
Robert E
RE
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Klein-Szanto
Andrés J P
AJ
Litwin
Samuel
S
Nicolas
Emmanuelle
E
Al-Jumaily
Raid
R
Alexander
Peter
P
Godwin
Andrew K
AK
Ross
Eric A
EA
Schilder
Russell J
RJ
Bassi
Daniel E
DE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005260:Female; D045683:Furin / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D045702:Proprotein Convertase 5 / Q000235:genetics / Q000378:metabolism; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate
C080654:PCSK6 protein, human; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C107583:proprotein convertase PC7; D045683:Furin