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S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis
Author(s) -
Németh Julia,
Stein Ilan,
Haag Daniel,
Riehl Astrid,
Longerich Thomas,
Horwitz Elad,
Breuhahn Kai,
Gebhardt Christoffer,
Schirmacher Peter,
Hahn Meinhard,
BenNeriah Yi,
Pikarsky Eli,
Angel Peter,
Hess Jochen
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23099
Subject(s) - carcinogenesis , cancer research , biology , inflammation , nfkb1 , s100a9 , s100a8 , nf κb , ectopic expression , cancer , cell culture , gene , immunology , transcription factor , genetics
The nuclear factor‐kappaB (NF‐κB) signaling pathway has been recently shown to participate in inflammation‐induced cancer progression. Here, we describe a detailed analysis of the NF‐κB–dependent gene regulatory network in the well‐established Mdr2 knockout mouse model of inflammation‐associated liver carcinogenesis. Expression profiling of NF‐κB–deficient and NF‐κB–proficient hepatocellular carcinoma (HCC) revealed a comprehensive list of known and novel putative NF‐κB 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‐κB 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. (H EPATOLOGY 2009.)