Systematic name M2279
Brief description Genes down-regulated in MEF cells (embryonic fibroblast) upon knockout of ATF2 [GeneID=1386].
Full description or abstract Transcription factor ATF-2 is a nuclear target of stress-activated protein kinases, such as p38, which are activated by various extracellular stresses, including UV light. Here, we show that ATF-2 plays a critical role in hypoxia- and high-cell-density-induced apoptosis and the development of mammary tumors. Compared to wild-type cells, Atf-2(-/-) mouse embryonic fibroblasts (MEFs) were more resistant to hypoxia- and anisomycin-induced apoptosis but remained equally susceptible to other stresses, including UV. Atf-2(-/-) and Atf-2(+/-) MEFs could not express a group of genes, such as Gadd45alpha, whose overexpression can induce apoptosis, in response to hypoxia. Atf-2(-/-) MEFs also had a higher saturation density than wild-type cells and expressed lower levels of Maspin, the breast cancer tumor suppressor, which is also known to enhance cellular sensitivity to apoptotic stimuli. Atf-2(-/-) MEFs underwent a lower degree of apoptosis at high cell density than wild-type cells. Atf-2(+/-) mice were highly prone to mammary tumors that expressed reduced levels of Gadd45alpha and Maspin. The ATF-2 mRNA levels in human breast cancers were lower than those in normal breast tissue. Thus, ATF-2 acts as a tumor susceptibility gene of mammary tumors, at least partly, by activating a group of target genes, including Maspin and Gadd45alpha.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17189429   Authors: Maekawa T,Shinagawa T,Sano Y,Sakuma T,Nomura S,Nagasaki K,Miki Y,Saito-Ohara F,Inazawa J,Kohno T,Yokota J,Ishii S
Exact source Table 1S
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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