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Expression of endoprotease furin, prohormone convertase (PC) 1/3 and PC2 in pulmonary neuroendocrine lesions: Correlation of functional differentiation of neuroendocrine cells with posttranslational processing of prohormones

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Abstract

Prohormone convertases (PCs) are key enzymes in the regulated pathway for the posttranslational processing of peptide hormones, whereas furin is a microsomal protease mediating the constitutive pathway of protein secretion in most secretory cells. To elucidate the relationship of the expression of these processing enzymes and cellular differentiation, we examined the localization of furin, PC1/3, and PC2 using immunohistochemistry andin situ hybridization in such pulmonary neuroendocrine lesions as bronchial carcinoids, pulmonary tumorlets, and small-cell carcinomas of the lung. PCs were commonly detected in the cytologically and functionally differentiated lesions, i.e., carcinoids and tumorlets with immunoreactivity for peptide products in secretory granules. However, PCs and hormones were absent in most of the cytologically less-differentiated lesions, i.e., small-cell carcinoma. Only a few malignant lesions showed focal peptide production. In contrast, furin was expressed in all the lesions, including small-cell carcinoma. It is suggested that furin functions in the poorly differentiated neuroendocrine tumor containing few secretory granules, by participating in the premature processing of peptide products. The lack of PCs should be a fundamental mechanism for the detection of prohormones in the serum of patients with small-cell carcinoma of the lung.

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Authors and Affiliations

  1. Department of Pathology, Tokai University School of Medicine, Bohseidai, 259-1193, Isehara, Kanagawa, Japan

    Hiroshi Kajiwara MD, Yoshiko Itoh PhD, Yutaka Tsutsumi MD & R. Yoshiyuki Osamura MD

  2. Department of Biology, Faculty of Science, Shizuoka University, Shizooka, Japan

    Shigeyasu Tanaka PhD

Authors
  1. Hiroshi Kajiwara MD
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  2. Shigeyasu Tanaka PhD
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  3. Yoshiko Itoh PhD
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  4. Yutaka Tsutsumi MD
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  5. R. Yoshiyuki Osamura MD
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Correspondence to Hiroshi Kajiwara MD.

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Kajiwara, H., Tanaka, S., Itoh, Y. et al. Expression of endoprotease furin, prohormone convertase (PC) 1/3 and PC2 in pulmonary neuroendocrine lesions: Correlation of functional differentiation of neuroendocrine cells with posttranslational processing of prohormones. Endocr Pathol 10, 85–94 (1999). https://doi.org/10.1007/BF02738819

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