Strong smooth muscle differentiation is dependent on myocardin gene amplification in most human retroperitoneal leiomyosarcomas.

Détails

ID Serval
serval:BIB_99D09E595701
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Strong smooth muscle differentiation is dependent on myocardin gene amplification in most human retroperitoneal leiomyosarcomas.
Périodique
Cancer Research
Auteur⸱e⸱s
Pérot G., Derré J., Coindre J.M., Tirode F., Lucchesi C., Mariani O., Gibault L., Guillou L., Terrier P., Aurias A.
ISSN
1538-7445[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
69
Numéro
6
Pages
2269-2278
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.
Mots-clé
Cell Differentiation, Cell Line, Tumor, Cell Movement, Chromosomes, Human, Pair 17, Gene Amplification, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Leiomyosarcoma, Muscle, Smooth, Nuclear Proteins, RNA, Small Interfering, Retroperitoneal Neoplasms, Trans-Activators, Up-Regulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/05/2009 17:39
Dernière modification de la notice
20/08/2019 15:01
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