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

Peptide hormones are generated by proteolytic processing of their respectiv e protein precursors by several prohormone processing proteases. The peptid e hormone PTHrP is widely expressed in normal and malignant tissues, where proPTHrP undergoes proteolytic processing to generate PTHrP peptides with d istinct biological actions. In this study, the tissue distribution of the p rohormone processing enzymes PTP, PC1, and PC2 were compared by immunohisto chemistry in human PTHrP-producing cancer cell lines, and in mammalian neur oendocrine and other tissues from rat and bovine that contain peptide hormo nes. PTP, PC1, and PC2 were prominently expressed in PTHrP-expressing human cancer cell lines originating from tumors of the breast, lung, prostate, a s well as lymphoma. These processing enzymes also showed significant expres sion in normal mammalian neuroendocrine tissues from bovine and rat, includ ing pituitary, hypothalamus, adrenal medulla, pancreas, and other tissues. Most neuroendocrine tissues contained prominent levels of at least two of t he three processing enzymes examined, and all tissues contained at least on e of these three enzymes. Differential expression of processing enzyme prot eins was also demonstrated by Western blots. The differential expression of PTP, PC1, and PC2 observed in certain cancer and normal neuroendocrine cel l types postulates selective roles for these processing enzymes in differen t tissues for generating biologically active peptide hormones. These result s support the importance of these processing enzymes in their hypothesized roles in prohormone processing.