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Endocr Pathol. 2000;11(1):31-39. doi: 10.1385/ep:11:1:31.

Proprotein-Processing Endoprotease Furin and its Substrate Parathyroid Hormone-Related Protein Are Coexpressed in Insulinoma Cells.

Endocrine pathology

Yoshie Sawada, Toru Kameya, Toru Aizama, Tetsuro Izumi, Toshiyuki Takeuchi

PMID: 12114655 DOI: 10.1385/ep:11:1:31

Abstract

Parathyroid hormone-related protein (PTHrP) is frequently produced in pancreatic endocrine tumors. PTHrP is synthesized as the precursor pro-PTHrP and undergoes a series of posttranslational processing reactions, among which cleavage of a 12 amino acid sequence from its precursor is crucial for the biological activation of PTHrP. This cleavage is catalyzed by furin, a proprotein-processing endoprotease that cleaves the consensus sequence -Arg-X-(Lys/Arg)-Arg-X-. We previously reported that furin is highly expressed in rat pancreatic islets during the perinatal stage and that the expression of furin in pancreatic-cells induces faster cell growth. From this, we postulated that furin may be co-expressed with PTHrP in insulinomas. We immunostained insulin, PTHrP, and furin in 21 human pancreatic endocrine tumors: 10 insulinomas, 5 VIPomas, 4 gastrinomas, and 2 somatostatinomas. Of these 21 endocrine tumors, furin was positively stained in all 10 insulinomas. Likewise, PTHrP was detected in the same insulinomas. We found one VIPoma and one gastrinoma contained a few insulin-positive cells scatteringly, which were also positive for furin and PTHrP. But other non-insulinoma endocrine tumors did not display furin and PTHrP positivity. We conclude that furin and its substrate pro-PTHrP are co-expressed specifically in insulinomas.

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