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This version published online on April 17, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0035
A more recent version of this article appeared on July 1, 2007
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Submitted on January 8, 2007
Accepted on April 9, 2007

PEPTIDE PRODUCTS OF THE NEUROTROPHIN-INDUCIBLE GENE vgf ARE PRODUCED IN HUMAN NEUROENDOCRINE CELLS FROM EARLY DEVELOPMENT, AND INCREASE IN HYPERPLASIA AND NEOPLASIA

Guido Rindi*, Lisa Licini, Vittorio Necchi, Lorena Bottarelli, Nicoletta Campanini, Cinzia Azzoni, Maurizio Favret, Giovanna Giordano, Filomena D'Amato, Carla Brancia, Enrico Solcia, and Gian-Luca Ferri

Department of Pathology and Laboratory Medicine, University of Parma, 43100 Parma, I; Surgical Pathology Service, Ospedale Leno-Manerbio, 25024 Leno (BS), I; Department of Human Pathology and Genetics, University of Pavia, 27100 Pavia, I; NEF-Laboratory, Department of Cytomorphology, University of Cagliari, 09042 Monserrato (CA), I

* To whom correspondence should be addressed. E-mail: guido.rindi{at}unipr.it.

Background: Although the neurotrophin (NT) inducible gene vgf is expressed in mammalian neurons and endocrine cells, limited data is available in man.

Aim: 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 proVGF422-430 and human proVGF298-306-NH2) and the proVGF C-Ter ending (human proVGF607-615). Developing and normal adult endocrine cells, hyperplastic endocrine lesions (thyroid, parathyroid, lung, stomach) and 120 tumors (102 endocrine) were studied. Immunogold electron microscopy was performed on normal, adult pancreas and gut, Western blotting 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 and gastrin cells and in 88 out of 102 endocrine tumors. At electron-microscopy proVGF immunoreactivity was restricted to electron dense granules. Western blotting revealed large MW forms and cleavage fragments in both control tissues and tumor extracts.

Conclusions: proVGF related peptides are present in endocrine cells early during development, adulthood and increase in hyperplasia and tumors; proVGF fragments could be novel diagnostic tools for endocrine cells and related lesions including tumors.




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F. D'Amato, B. Noli, C. Brancia, C. Cocco, G. Flore, M. Collu, P. Nicolussi, and G.-L. Ferri
Differential distribution of VGF-derived peptides in the adrenal medulla and evidence for their selective modulation
J. Endocrinol., May 1, 2008; 197(2): 359 - 369.
[Abstract] [Full Text] [PDF]


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