Human Gene Set: SNF5_DN.V1_DN


Standard name SNF5_DN.V1_DN
Systematic name M2715
Brief description Genes down-regulated in MEF cells (embryonic fibroblasts) with knockout of SNF5 [GeneID=6598] gene.
Full description or abstract Snf5 (Ini1/Baf47/Smarcb1), a core member of the Swi/Snf chromatin remodeling complex, is a potent tumor suppressor whose mechanism of action is largely unknown. Biallelic loss of Snf5 leads to the onset of aggressive cancers in both humans and mice. We have developed an innovative and widely applicable analytical technique for cross-species validation of cancer models and show that the gene expression profiles of our Snf5 murine models closely resemble those of human Snf5-deficient rhabdoid tumors. We exploit this system to produce what we believe to be the first report documenting the effects on gene expression of inactivating a Swi/Snf subunit in normal mammalian cells and to identify the transcriptional pathways regulated by Snf5. We demonstrate that the tumor suppressor activity of Snf5 depends on its regulation of cell cycle progression; Snf5 inactivation leads to aberrant up-regulation of E2F targets and increased levels of p53 that are accompanied by apoptosis, polyploidy, and growth arrest. Further, conditional mouse models demonstrate that inactivation of p16Ink4a or Rb (retinoblastoma) does not accelerate tumor formation in Snf5 conditional mice, whereas mutation of p53 leads to a dramatic acceleration of tumor formation.
Collection C6: Oncogenic Signature
Source publication Pubmed 16301525   Authors: Isakoff MS,Sansam CG,Tamayo P,Subramanian A,Evans JA,Fillmore CM,Wang X,Biegel JA,Pomeroy SL,Mesirov JP,Roberts CW
Exact source SNF5- vs Controls; bottom 200 genes (diff. of means)
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Source species Mus musculus
Contributed by Pablo Tamayo (Broad Institute)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 7.1: Fixed RIKEN identifiers.

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