title: S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis.
abstract: The nuclear factor-kappaB (NF-kappaB) signaling pathway has been recently shown to participate in inflammation-induced cancer progression. Here, we describe a detailed analysis of the NF-kappaB-dependent gene regulatory network in the well-established Mdr2 knockout mouse model of inflammation-associated liver carcinogenesis. Expression profiling of NF-kappaB-deficient and NF-kappaB-proficient hepatocellular carcinoma (HCC) revealed a comprehensive list of known and novel putative NF-kappaB target genes, including S100a8 and S100a9. We detected increased co-expression of S100A8 and S100A9 proteins in mouse HCC cells, in human HCC tissue, and in the HCC cell line Hep3B on ectopic RelA expression. Finally, we found a synergistic function for S100A8 and S100A9 in Hep3B cells resulting in a significant induction of reactive oxygen species (ROS), accompanied by enhanced cell survival.
  
  
  CONCLUSIONS
  We identified S100A8 and S100A9 as novel NF-kappaB target genes in HCC cells during inflammation-associated liver carcinogenesis and provide experimental evidence that increased co-expression of both proteins supports malignant progression by activation of ROS-dependent signaling pathways and protection from cell death.
authors: Division of Signal Transduction and Growth Control (A100), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors: Julia
authors: J
authors: Németh
authors: Ilan
authors: I
authors: Stein
authors: Daniel
authors: D
authors: Haag
authors: Astrid
authors: A
authors: Riehl
authors: Thomas
authors: T
authors: Longerich
authors: Elad
authors: E
authors: Horwitz
authors: Kai
authors: K
authors: Breuhahn
authors: Christoffer
authors: C
authors: Gebhardt
authors: Peter
authors: P
authors: Schirmacher
authors: Meinhard
authors: M
authors: Hahn
authors: Yinon
authors: Y
authors: Ben-Neriah
authors: Eli
authors: E
authors: Pikarsky
authors: Peter
authors: P
authors: Angel
authors: Jochen
authors: J
authors: Hess
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism*; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D040501:Calgranulin A; D040502:Calgranulin B; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000097202:ATP-Binding Cassette Sub-Family B Member 4