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Proprotein-processing endoprotease furin and its substrate parathyroid hormone-related protein are coexpressed in insulinoma cells

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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 β 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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Authors and Affiliations

  1. Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi, 371-8512, Maebashi, Japan

    Yoshie Sawada MD, Tetsuro Izumi MD & Toshiyuki Takeuchi MD

  2. Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan

    Toru Kameya MD

  3. Department of Gerontology, Shinshu University School of Medicine, Marsumoto, Japan

    Toru Aizawa MD

Authors
  1. Yoshie Sawada MD
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  2. Toru Kameya MD
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  3. Toru Aizawa MD
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  4. Tetsuro Izumi MD
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  5. Toshiyuki Takeuchi MD
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Correspondence to Toshiyuki Takeuchi MD.

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Sawada, Y., Kameya, T., Aizawa, T. et al. Proprotein-processing endoprotease furin and its substrate parathyroid hormone-related protein are coexpressed in insulinoma cells. Endocr Pathol 11, 31–39 (2000). https://doi.org/10.1385/EP:11:1:31

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