Gene Set: BOWIE_RESPONSE_TO_EXTRACELLULAR_MATRIX

Standard name BOWIE_RESPONSE_TO_EXTRACELLULAR_MATRIX
Systematic name M6162
Brief description Genes up-regulated by growing HMEC-E6 cells (mammary epithelial cells damaged by expression of HPV-16 E6 [GeneID=1489078]) in extracellular matrix (ECM).
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17016442   Authors: Bowie ML,Troch MM,Delrow J,Dietze EC,Bean GR,Ibarra C,Pandiyan G,Seewaldt VL
Exact source Table 1: ECM HMEC-E6
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(show 3 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HuGene
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Version history 3.0: First introduced

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