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Eur J Cancer. 2006 Sep;42(14):2326-34.

The tumour suppressor hSNF5/INI1 controls the differentiation potential of malignant rhabdoid cells.

Author information

1
INSERM U509, Laboratoire de Pathologie Mol├ęculaire des Cancers, Institut Curie, 26 rue d'Ulm, 75248 Paris, France.

Abstract

Malignant rhabdoid tumours (MRT) are highly aggressive cancers of early childhood that arise in different organs or tissues. The unifying criterion for these tumours is the presence of inactivating mutations of the hSNF5/INI1 tumour suppressor gene which encodes a core subunit of the chromatin remodelling SWI/SNF complex. Using a variety of markers we analysed the phenotypic traits of MON and DEV cell lines derived respectively from an undifferentiated abdominal MRT and from a brain MRT. DEV cells express spontaneously a wide range of neural and glial markers. It can be induced to differentiate into the neural lineage following hSNF5/INI1 expression with appearance of neurite processes, strong increase of neural markers and decrease of glial markers. A less pronounced neural differentiation is also observed with MON cells, which possess more primitive polyphenotypic features with positivity for markers from the three embryonic layers. Finally, we show that the neural differentiation of rat PC12 cells in the presence of nerve growth factor (NGF) is strongly impaired when hSNF5/INI1 expression is inhibited by RNA interference. Altogether these results indicate that hSNF5/INI1 is an essential subunit for SWI/SNF-dependant induction of neural differentiation programs. Further experiments should enable documentation of whether it provides instructive or permissive signals for differentiation.

PMID:
16908131
DOI:
10.1016/j.ejca.2006.03.028
[Indexed for MEDLINE]

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