Gene Set: HENDRICKS_SMARCA4_TARGETS_DN

Standard name HENDRICKS_SMARCA4_TARGETS_DN
Systematic name M7914
Brief description Genes down-regulated in ALAB cells (breast cancer) upon reintroduction of SMARCA4 [GeneID=6597] expressed off adenoviral vector.
Full description or abstract Human BRG1, a subunit of the Swi/Snf chromatin remodeling apparatus, has been implicated in regulation of cellular proliferation and is a candidate tumor suppressor. Reintroduction of BRG1 into a breast tumor cell line, ALAB, carrying a defined mutation in the BRG1 gene, induced growth arrest. Gene expression data revealed that the arrest may in part be accounted for by down-regulation of select E2F target genes such as cyclin E, but more dramatically, by up-regulation of mRNAs for the cyclin-dependent kinase inhibitors p21 and p15. Protein levels of both p15 and p21 were induced, and p21 protein was recruited to a complex with cyclin-dependent kinase, CDK2, to inhibit its activity. BRG1 can associate with the p21 promoter in a p53-independent manner, suggesting that the induction of p21 by BRG1 may be direct. Further, using microarray and real-time PCR analysis we identified several novel BRG1-regulated genes. Our work provides further evidence for a role for BRG1 in the regulation of several genes involved in key steps in tumorigenesis and has revealed a potential mechanism for BRG1-induced growth arrest.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 14673169   Authors: Hendricks KB,Shanahan F,Lees E
Exact source Table A1: repressed
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Organism Homo sapiens
Contributed by John Newman (University of Washington)
Source platform HUMAN_SEQ_ACCESSION
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Version history 3.0: Renamed from BRG1_ALAB_DN

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