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- Title
The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors.
- Authors
Caramel, J; Medjkane, S; Quignon, F; Delattre, O
- 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/EBPβ and PPARγ2 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.Oncogene (2008) 27, 2035–2044; doi:10.1038/sj.onc.1210847; published online 8 October 2007
- Subjects
FAT cells; TUMORS; CELL differentiation; ADENOSINE triphosphate; CELL lines; CELL cycle; STEM cells
- Publication
Oncogene, 2008, Vol 27, Issue 14, p2035
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210847