title: Peptide products of the neurotrophin-inducible gene vgf are produced in human neuroendocrine cells from early development and increase in hyperplasia and neoplasia.
abstract: BACKGROUND
  Although the neurotrophin-inducible gene vgf is expressed in mammalian neurons and endocrine cells, limited data is available in man.
  
  
  OBJECTIVE
  The objective of the study was to map proVGF peptides in human endocrine cells during development, adulthood, hyperplasia, and tumors.
  
  
  METHODS
  Antisera were generated against peptides related to internal cleavage or cleavage-amidation sites (rat proVGF(422-430) and human proVGF(298-306)-NH2) and the proVGF C-terminal ending (human proVGF(607-615)). Developing and normal adult endocrine cells, hyperplastic endocrine lesions (thyroid, parathyroid, lung, and stomach), and 120 tumors (102 endocrine) were studied. Immunogold electron microscopy was performed on normal adult pancreas and gut, and Western blotting was performed on extracts of control tissues and endocrine tumors.
  
  
  RESULTS
  proVGF fragments were revealed in developing pituitary, gut, pancreas, and adrenal medulla from 10 gestational weeks, in normal adult pituitary and adrenal medulla, pancreatic glucagon, and insulin cells and gut serotonin cells, in hyperplastic thyroid calcitonin cells, lung P cells, gastric enterochromaffin-like cells, and gastrin cells, and in 88 of 102 endocrine tumors. At electron microscopy proVGF immunoreactivity was restricted to electron-dense granules. Western blotting revealed large molecular weight forms and cleavage fragments in both control tissues and tumor extracts.
  
  
  CONCLUSIONS
  proVGF-related peptides are present in endocrine cells early during development and adulthood and increase in hyperplasia and tumors, and proVGF fragments could be novel diagnostic tools for endocrine cells and related lesions, including tumors.
authors: Department of Pathology and Laboratory Medicine, University of Parma, 43100 Parma, Italy. guido.rindi@unipr.it
authors: Guido
authors: G
authors: Rindi
authors: Lisa
authors: L
authors: Licini
authors: Vittorio
authors: V
authors: Necchi
authors: Lorena
authors: L
authors: Bottarelli
authors: Nicoletta
authors: N
authors: Campanini
authors: Cinzia
authors: C
authors: Azzoni
authors: Maurizio
authors: M
authors: Favret
authors: Giovanna
authors: G
authors: Giordano
authors: Filomena
authors: F
authors: D'Amato
authors: Carla
authors: C
authors: Brancia
authors: Enrico
authors: E
authors: Solcia
authors: Gian-Luca
authors: GL
authors: Ferri
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D004701:Endocrine Gland Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004703:Endocrine System / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D009414:Nerve Growth Factors / Q000378:metabolism*; D010235:Paraganglioma / Q000378:metabolism / Q000473:pathology; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology
chemical_list: D009414:Nerve Growth Factors; C510637:VGF protein, human