STANDARD_NAME	BOWIE_RESPONSE_TO_EXTRACELLULAR_MATRIX
SYSTEMATIC_NAME	M6162
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BOWIE_RESPONSE_TO_EXTRACELLULAR_MATRIX
NAMESPACE	AFFY_HuGene
DESCRIPTION_BRIEF	Genes up-regulated by growing HMEC-E6 cells (mammary epithelial cells damaged by expression of HPV-16 E6 [GeneID=1489078]) in extracellular matrix (ECM).
DESCRIPTION_FULL	Interactions between extracellular matrix (ECM) and mammary epithelial cells are critical for mammary gland homeostasis and apoptotic signaling. Interferon regulatory factor-1 (IRF-1) is a transcriptional regulator that promotes apoptosis during mammary gland involution and p53-independent apoptosis. We have recently shown that rapid cell surface tamoxifen (Tam) signaling promotes apoptosis in normal human mammary epithelial cells that were acutely damaged by expression of human papillomavirus type-16 E6 protein (*HMEC-E6). Apoptosis was mediated by recruitment of CREB-binding protein (CBP) to the gamma-activating sequence (GAS) element of the IRF-1 promoter, induction of IRF-1 and caspase-1/-3 activation. Here, we show that growth factor-depleted, reconstituted ECM (rECM), similar to Tam, promotes apoptosis in *HMEC-E6 cells through induction of IRF-1. Apoptosis was temporally associated with recruitment of CBP to the GAS element of the IRF-1 promoter, induction of IRF-1 expression and caspase-1/-3 activation. Small interfering RNA-mediated suppression of IRF-1 protein expression in *HMEC-E6 cells blocked (1) induction of IRF-1, (2) caspase-1/-3 activation and (3) apoptosis. These observations demonstrate that IRF-1 promotes rECM-mediated apoptosis and provide evidence that both rECM and rapid Tam signaling transcriptionally activate IRF-1 through recruitment of CBP to the IRF-1 GAS promoter complex.
PMID	17016442
GEOID	
AUTHORS	Bowie ML,Troch MM,Delrow J,Dietze EC,Bean GR,Ibarra C,Pandiyan G,Seewaldt VL
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1: ECM HMEC-E6
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	J04164_at,L05072_s_at,M13755_at,M14660_at,M24594_at,M33882_at,M63838_s_at,M97936_at,U19247_rna1_s_at,U22970_rna1_s_at,U52513_at,U53830_at,U72882_s_at,X02874_at,X02875_s_at,X66401_cds1_at,X71874_cds1_at,Z14982_rna1_at
GENE_SYMBOLS	IFITM1,IRF1,ISG15,IFIT2,IFIT1,MX1,IFI16,STAT1,IFNGR1,IFI6,IFIT3,IRF7,IFI35,OAS1,OAS1,PSMB9,PSMB10,PSMB8
FOUNDER_NAMES