S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis
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S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis. / Németh, Julia; Stein, Ilan; Haag, Daniel; Riehl, Astrid; Longerich, Thomas; Horwitz, Elad; Breuhahn, Kai; Gebhardt, Christoffer; Schirmacher, Peter; Hahn, Meinhard; Ben-Neriah, Yinon; Pikarsky, Eli; Angel, Peter; Hess, Jochen.
in: HEPATOLOGY, Jahrgang 50, Nr. 4, 10.2009, S. 1251-62.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis
AU - Németh, Julia
AU - Stein, Ilan
AU - Haag, Daniel
AU - Riehl, Astrid
AU - Longerich, Thomas
AU - Horwitz, Elad
AU - Breuhahn, Kai
AU - Gebhardt, Christoffer
AU - Schirmacher, Peter
AU - Hahn, Meinhard
AU - Ben-Neriah, Yinon
AU - Pikarsky, Eli
AU - Angel, Peter
AU - Hess, Jochen
PY - 2009/10
Y1 - 2009/10
N2 - UNLABELLED: 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.CONCLUSION: 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.
AB - UNLABELLED: 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.CONCLUSION: 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.
KW - ATP Binding Cassette Transporter, Sub-Family B
KW - Animals
KW - Apoptosis
KW - Calgranulin A
KW - Calgranulin B
KW - Carcinoma, Hepatocellular
KW - Cell Line, Tumor
KW - Disease Models, Animal
KW - Humans
KW - Liver Neoplasms
KW - Mice
KW - Mice, Knockout
KW - Mice, Transgenic
KW - NF-kappa B
KW - Reactive Oxygen Species
KW - Signal Transduction
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/hep.23099
DO - 10.1002/hep.23099
M3 - SCORING: Journal article
C2 - 19670424
VL - 50
SP - 1251
EP - 1262
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 4
ER -