title: 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.
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 neuroendocrine 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 other tissues. 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. These results support the importance of these processing enzymes in their hypothesized roles in prohormone processing.
authors.affiliation: Dept of Medicine, San Diego VA Medical Center, University of California, La Jolla 92093-0822, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Deftos
authors.forename: D
authors.initials: D
authors.lastname: Burton
authors.forename: R H
authors.initials: RH
authors.lastname: Hastings
authors.forename: R
authors.initials: R
authors.lastname: Terkeltaub
authors.forename: V Y
authors.initials: VY
authors.lastname: Hook
mesh_terms: D000313:Adrenal Medulla / Q000201:enzymology; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000032:analysis*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000201:enzymology; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology; D008223:Lymphoma / Q000201:enzymology; D008297:Male; D009490:Neurosecretory Systems / Q000201:enzymology*; D010179:Pancreas / Q000201:enzymology; D044162:Parathyroid Hormone-Related Protein; D010902:Pituitary Gland / Q000201:enzymology; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D011471:Prostatic Neoplasms / Q000201:enzymology; D014176:Protein Biosynthesis; D051381:Rats; D013381:Subtilisins / Q000032:analysis*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D003546:Cysteine Endopeptidases; C083275:prohormone thiol protease; D016282:Aspartic Acid Endopeptidases