Human Gene Set: RADAEVA_RESPONSE_TO_IFNA1_DN


Standard name RADAEVA_RESPONSE_TO_IFNA1_DN
Systematic name M19208
Brief description Genes down-regulated in primary hepatocytes and Hep3B (hepatocyte) cells in response to IFNA [GeneID=3439].
Full description or abstract BACKGROUND & AIMS: Interferon (IFN)-alpha therapy is currently the primary choice for viral hepatitis and a promising treatment for hepatocellular carcinoma (HCC). Primary mouse and rat hepatocytes respond poorly to IFN-alpha stimulation. Thus, it is very important to examine the IFN-alpha signal pathway in primary human hepatocytes. METHODS: The IFN-alpha-activated signals and genes in primary human hepatocytes and hepatoma cells were examined by Western blotting and microarray analyses. RESULTS: Primary human hepatocytes respond very well to IFN-alpha stimulation as shown by activation of multiple signal transducer and activator of transcription factor (STAT) 1, 2, 3, 5, and multiple genes. The differential response to IFN-alpha stimulation in primary human and mouse hepatocytes may be caused by expression of predominant functional IFN-alpha receptor 2c (IFNAR2c) in primary human hepatocytes vs. expression of predominant inhibitory IFNAR2a in mouse hepatocytes. Microarray analyses of primary human hepatocytes show that IFN-alpha up-regulates about 44 genes by over 2-fold and down-regulates about 9 genes by 50%. The up-regulated genes include a variety of antiviral and tumor suppressors/proapoptotic genes. The down-regulated genes include c-myc and c-Met, the hepatocyte growth factor (HGF) receptor. Down-regulation of c-Met is caused by IFN-alpha suppression of the c-Met promoter through down-regulation of Sp1 binding and results in attenuation of HGF-induced signals and cell proliferation. CONCLUSIONS: IFN-alpha directly targets human hepatocytes, followed by activation of multiple STATs and regulation of a wide variety of genes, which may contribute to the antiviral and antitumor activities of IFN-alpha in human liver.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 11910354   Authors: Radaeva S,Jaruga B,Hong F,Kim WH,Fan S,Cai H,Strom S,Liu Y,El-Assal O,Gao B
Exact source Table 2
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Source species Homo sapiens
Contributed by Yujin Hoshida (Broad Institute)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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