title: Proprotein convertases in post-menopausal endometrial cancer: distinctive regulation and non-invasive diagnosis.
abstract: Proprotein convertases (PCs) play critical roles in cleaving precursor proteins (growth factors, hormones, receptors and adhesion molecules) for activation. PCs are implicated in a number of cellular functions, including oncogenesis. Endometrial cancer is the most common gynecological cancer in the developed world, but the involvement of PCs is unclear. To characterize the role of PCs in endometrial cancer, we assessed expression of seven PCs (PC1/3, PC2, PACE4, PC4, furin, PC5/6 and PC7) by RT-PCR in six well characterized endometrial cancer cell lines. Expression was variable in all lines, with furin being most consistently expressed in all cell lines tested. We next determined the cellular localization and expression levels of four ubiquitously expressed PCs (furin, PACE4, PC5/6 and PC7) in post-menopausal endometrial biopsies from control (n=7) and endometrial cancer patients (n=30) by immunohistochemistry. Furin increased in tumors, whereas PC5/6, PACE4 and PC7 expression was reduced with increasing cancer grades. Uterine lavage is a non-invasive source material for evaluating the endometrium. We thus assessed whether total PC activity was altered in uterine lavage of endometrial cancer patients (n=36) compared to controls (n=10). PC activity was detected in all uterine lavage samples, and significantly elevated in all grades of endometrial cancer. This study demonstrates a complex association between individual PCs and endometrial cancer. Importantly, we show that monitoring the total PC activity in uterine lavage may provide a rapid and non-invasive method for the diagnosis of endometrial cancer in postmenopausal women.
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.
authors.forename: Harmeet
authors.initials: H
authors.lastname: Singh
authors.forename: Sophea
authors.initials: S
authors.lastname: Heng
authors.forename: Peter K
authors.initials: PK
authors.lastname: Nicholls
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Li Tsan
authors.initials: LT
authors.lastname: Tai
authors.forename: Tom
authors.initials: T
authors.lastname: Jobling
authors.forename: Lois A
authors.initials: LA
authors.lastname: Salamonsen
authors.forename: Guiying
authors.initials: G
authors.lastname: Nie
mesh_terms: D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D017698:Postmenopause; D043484:Proprotein Convertases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D043484:Proprotein Convertases