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Comparative tissue distribution of the processing enzymes “prohormone thiol protease”, and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocine tissues

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Abstract

Peptide hormones are generated by proteolytic processing of their respective protein precursors by several prohormone processing proteases. The peptide hormone PTHrP is widely expressed in normal and malignant tissues, where proPTHrP undergoes proteolytic processing to generate PTHrp peptides with distinct biological actions. In this study, the tissue distribution of the prohormone processing enzymes PTP, PC1, and PC2 were compared by immunohistochemistry in human PTHrP-producing cancer cell lines, and in mammalian neuroedocrine and other tissues from rat and bovine that contain peptide hormones. PTP, PC1, and PC2 were prominently expressed in PTHrP-expressing human cancer cell lines originating from tumors of the breast, lung prostate, as well as lymphoma. These processing enzymes also showed significant expression in normal mammalian neuroendocrine tissues from bovine and rat, including pituitary, hypothalamus, adrenal medulla, pancreas, and oter tissue. Most neuroendocrine tissues contained prominent levels of at least two of the three processing enzymes examined, and all tissues contained at least one of these three enzymes. Differential expression of processing enzyme proteins was also demonstrated by Western blots. The differential expression of PTP, PC1 and PC2 observed in certain cancer and normal neuroendocrine cell types postulates selective roles for these processing enzymes in different tissues for generating biologically active peptide hormones. Theses results support the importnce of these processing enzymes in their hypothesized roles in prohormone processing.

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Authors and Affiliations

  1. Dept. of Medicine, University of California, 92093-0822, San Diego, La Jolla, CA

    Leonard J. Deftos, Douglas Burton & Robert Terkeltaub

  2. Dept. of Neurosciences, University of California, 92093-0822, San Diego, La Jolla, CA

    Leonard J. Deftos, Douglas Burton & Robert Terkeltaub

  3. Dept. of Anesthesiology, University of California, 92093-0822, San Diego, La Jolla, CA

    Randolph H. Hastings & Vivian Y. H. Hook

  4. Buck Institute for Age Research, 8001 Redwood Blvd., 94945, Novato, CA

    Vivian Y. H. Hook

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  1. Leonard J. Deftos
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  2. Douglas Burton
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  3. Randolph H. Hastings
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  4. Robert Terkeltaub
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  5. Vivian Y. H. Hook
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Correspondence to Vivian Y. H. Hook.

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Deftos, L.J., Burton, D., Hastings, R.H. et al. Comparative tissue distribution of the processing enzymes “prohormone thiol protease”, and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocine tissues. Endocr 15, 217–224 (2001). https://doi.org/10.1385/ENDO:15:2:217

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  • DOI: https://doi.org/10.1385/ENDO:15:2:217

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