Human Gene Set: NAGASHIMA_NRG1_SIGNALING_DN


Standard name NAGASHIMA_NRG1_SIGNALING_DN
Systematic name M17600
Brief description Genes down-regulated in MCF7 cells (breast cancer) after stimulation with NRG1 [GeneID=3084].
Full description or abstract ErbB receptor ligands, epidermal growth factor (EGF) and heregulin (HRG), induce dose-dependent transient and sustained intracellular signaling, proliferation, and differentiation of MCF-7 breast cancer cells, respectively. In an effort to delineate the ligand-specific cell determination mechanism, we investigated time course gene expressions induced by EGF and HRG that induce distinct cellular phenotypes in MCF-7 cells. To analyze independently the effects of ligand dosage and time for gene expression, we developed a statistical method for estimating the two effects. Our results indicated that signal transduction pathways convey quantitative properties of the dose-dependent activation of ErbB receptor to early transcription. The results also implied that moderate changes in the expression levels of a number of genes, not the predominant regulation of a few specific genes, might cooperatively work at the early stage of the transcription for determining cell fate. However, the EGF- and HRG-induced distinct signal durations resulted in the ligand-oriented biphasic induction of proteins after 20 min. The selected gene list and HRG-induced prolonged signaling suggested that transcriptional feedback to the intracellular signaling results in a graded to biphasic response in the cell determination process and that each ErbB receptor is inextricably responsible for the control of amplitude and duration of cellular biochemical reactions.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17142811   Authors: Nagashima T,Shimodaira H,Ide K,Nakakuki T,Tani Y,Takahashi K,Yumoto N,Hatakeyama M
Exact source Table 1S: HRG fold change -
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced


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