1. ¹Institut Curie, Research Section, Paris, France
2. ²INSERM U830, Unité de Génétique et Biologie des Cancers, Paris, France

Correspondence: Dr O Delattre, Section de Recherche, Unité de Génétique et Biologie des Cancers, INSERM U830-Institut Curie, 26 rue d'Ulm, lle de France, 75248 Paris cedex 05, France. E-mail: olivier.delattre@curie.fr

³Current address: Transcription Laboratory, Cancer Research UK—London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

Received 18 April 2007; Revised 30 July 2007; Accepted 7 September 2007; Published online 8 October 2007.

Abstract

ATP-dependent SWI/SNF chromatin remodeling complexes regulate cell-cycle and play critical roles in a variety of differentiation pathways. The core subunit SNF5/INI1 is a tumor suppressor that is inactivated in a highly aggressive childhood cancer of unknown cellular origin, termed malignant rhabdoid tumor (MRT). The highly undifferentiated phenotype of this tumor suggests that the loss-of-function of hSNF5/INI1 impairs specific differentiation programs of the MRT parental cell. Based on the hypothesis that these programs might be reinitialized upon hSNF5/INI1 re-expression in MRTs, we show that some MRT cell lines can differentiate toward the adipogenic lineage. We further show that the knock down of the SNF5/INI1 subunit abrogates adipocyte differentiation of murine 3T3-L1 preadipocytes and of human mesenchymal stem cells. Finally, we provide evidence that hSNF5/INI1 cooperates with C/EBP and PPAR2 transcriptional regulators to activate the expression of adipocyte-specific genes. These data indicate that not only the ATPase subunit of the SWI/SNF complex, but also SNF5/INI1 is required for adipocyte differentiation. They further show that MRT cell lines harbor an adipogenic differentiation potential and that the tumor suppressor role of the SNF5/INI1 subunit may rely on its ability to regulate the balance between cell proliferation and differentiation.