Expression and processing of the neuroendocrine protein secretogranin II in benign and malignant pheochromocytomas.

Johann Guillemot (1) , Laure Barbier (1, 2) , Erwan Thouennon (1) , Virginie Vallet-Erdtmann (3) , Maite Montero-Hadjadje (1) , Herve Lefebvre (1, 4) , Marc Klein (5, 6) , Mihaela Muresan (6) , Pierre-François Plouin (7) , Nabil Seidah (8) , Hubert Vaudry (1, 9) , Youssef Anouar (1) , Laurent Yon (1)

1 Neuroendocrinologie cellulaire et moléculaire
2 CRSSA - Centre de Recherches du Service de Santé des Armées
3 GERHM - Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes
4 UPTE - Physiopathologie et Toxicologie Expérimentales
5 MoDyCo - Modèles, Dynamiques, Corpus
6 Department of Endocrinology
7 Service de médecine vasculaire et hypertension artérielle [CHU HEGP]
8 Laboratory of Biochemical Neuroendocrinology
9 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides

The aim of the present study was to compare the expression levels of secretogranin II (SgII), prohormone convertases (PC)1 and PC2, and the proteolytic processing of SgII in benign versus malignant pheochromocytomas. Quantitative (Q)-PCR experiments indicated that SgII, PC1, and PC2 mRNAs were overexpressed in pheochromocytoma compared to non-tumoral chromaffin cells (P<0.001) and in benign compared to malignant tumors (P<0.01). Western blot analysis using a human SgII antiserum revealed the occurrence of a 97-kDa band corresponding to the expected size of SgII, with significantly higher quantities in benign than in malignant tumors (P<0.05). Using antisera directed against sequential regions of SgII (N-terminal, secretoneurin [SN], EM66, internal, and C-terminal sequences), we observed distinct processing profiles between benign and malignant pheochromocytomas. In contrast, using PC1 and PC2 antisera no differences between the two types of tumors were found. RIA measurement showed that EM66 median values between benign and malignant chromaffin cell tumors were significantly different (128.5 vs. 6.3 ng/mg protein, respectively; P<0.001). Taken together, these results indicate that, in pheochromocytoma, malignancy is associated with reduced PC1, PC2, and SgII mRNA expression and decreased levels of processing products of SgII, in line with the low concentrations of EM66 that occur in malignant tumors. These data support the notion that SgII-processing products, such as EM66, could represent prognostic markers of pheochromocytomas.

Mots clés: EM66; pheochromocytoma; proteolytic processing; secretogranin II; malignancy; neuroendocrine tumor

Domaines: Biochimie, Biologie Moléculaire

Johann Guillemot, Laure Barbier, Erwan Thouennon, Virginie Vallet-Erdtmann, Maite Montero-Hadjadje, et al.. Expression and processing of the neuroendocrine protein secretogranin II in benign and malignant pheochromocytomas.. Annals of the New York Academy of Sciences, 2006, 1073, pp.527-32. ⟨10.1196/annals.1353.056⟩. ⟨hal-00653225⟩