Titre
Strong smooth muscle differentiation is dependent on myocardin gene amplification in most human retroperitoneal leiomyosarcomas.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Pérot, G.
Auteure/Auteur
Derré, J.
Auteure/Auteur
Coindre, J.M.
Auteure/Auteur
Tirode, F.
Auteure/Auteur
Lucchesi, C.
Auteure/Auteur
Mariani, O.
Auteure/Auteur
Gibault, L.
Auteure/Auteur
Guillou, L.
Auteure/Auteur
Terrier, P.
Auteure/Auteur
Aurias, A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1538-7445[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
69
Numéro
6
Première page
2269
Dernière page/numéro d’article
2278
Langue
anglais
Résumé
Myocardin (MYOCD), a serum response factor (SRF) transcriptional cofactor, is essential for cardiac and smooth muscle development and differentiation. We show here by array-based comparative genomic hybridization, fluorescence in situ hybridization, and expression analysis approaches that MYOCD gene is highly amplified and overexpressed in human retroperitoneal leiomyosarcomas (LMS), a very aggressive well-differentiated tumor. MYOCD inactivation by shRNA in a human LMS cell line with MYOCD locus amplification leads to a dramatic decrease of smooth muscle differentiation and strongly reduces cell migration. Moreover, forced MYOCD expression in three undifferentiated sarcoma cell lines and in one liposarcoma cell line confers a strong smooth muscle differentiation phenotype and increased migration abilities. Collectively, these results show that human retroperitoneal LMS differentiation is dependent on MYOCD amplification/overexpression, suggesting that in these well-differentiated LMS, differentiation could be a consequence of an acquired genomic alteration. In this hypothesis, these tumors would not necessarily derive from cells initially committed to smooth muscle differentiation. These data also provide new insights on the cellular origin of these sarcomas and on the complex connections between oncogenesis and differentiation in mesenchymal tumors.
PID Serval
serval:BIB_99D09E595701
PMID
Open Access
Oui
Date de création
2009-05-18T16:39:07.901Z
Date de création dans IRIS
2025-05-21T04:50:48Z