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Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma

(2007) CANCER CELL. 11(2). p.119-132
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Abstract
he licB kinase (IKK) subunit NEMO/IKK gamma is essential for activation of the transcription factor NF-kappa B, which regulates cellular responses to inflammation. The function of NEMO in the adult liver remains elusive. Here we show that ablation of NEMO in liver parenchymal cells caused the spontaneous development of hepatocellular carcinoma in mice. Tumor development was preceded by chronic liver disease resembling human nonalcoholic steatohepatitis (NASH). Antioxidant treatment and genetic ablation of FADD demonstrated that death receptor-mediated and oxidative stress-dependent death of NEMO-deficient hepatocytes triggered disease pathogenesis in this model. These results reveal that NEMO-mediated NF-kappa B activation in hepatocytes has an essential physiological function to prevent the spontaneous development of steatohepatitis and hepatocellular carcinoma, identifying NEMO as a tumor suppressor in the liver.
Keywords
INCONTINENTIA PIGMENTI, NF-KAPPA-B, DEFICIENT MICE, TNF-ALPHA, IKK-BETA, EMBRYONIC LETHALITY, KINASE IKK, APOPTOSIS, DEATH, DEGENERATION

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Chicago
Luedde, Tom, Naiara Beraza, Vasileios Kotsikoris, Geert van Loo, Arianna Nenci, Rita De Vos, Tania Roskams, Christian Trautwein, and Manolis Pasparakis. 2007. “Deletion of NEMO/IKKγ in Liver Parenchymal Cells Causes Steatohepatitis and Hepatocellular Carcinoma.” Cancer Cell 11 (2): 119–132.
APA
Luedde, T., Beraza, N., Kotsikoris, V., van Loo, G., Nenci, A., De Vos, R., Roskams, T., et al. (2007). Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. CANCER CELL, 11(2), 119–132.
Vancouver
1.
Luedde T, Beraza N, Kotsikoris V, van Loo G, Nenci A, De Vos R, et al. Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. CANCER CELL. 2007;11(2):119–32.
MLA
Luedde, Tom, Naiara Beraza, Vasileios Kotsikoris, et al. “Deletion of NEMO/IKKγ in Liver Parenchymal Cells Causes Steatohepatitis and Hepatocellular Carcinoma.” CANCER CELL 11.2 (2007): 119–132. Print.
@article{1202753,
  abstract     = {he licB kinase (IKK) subunit NEMO/IKK gamma is essential for activation of the transcription factor NF-kappa B, which regulates cellular responses to inflammation. The function of NEMO in the adult liver remains elusive. Here we show that ablation of NEMO in liver parenchymal cells caused the spontaneous development of hepatocellular carcinoma in mice. Tumor development was preceded by chronic liver disease resembling human nonalcoholic steatohepatitis (NASH). Antioxidant treatment and genetic ablation of FADD demonstrated that death receptor-mediated and oxidative stress-dependent death of NEMO-deficient hepatocytes triggered disease pathogenesis in this model. These results reveal that NEMO-mediated NF-kappa B activation in hepatocytes has an essential physiological function to prevent the spontaneous development of steatohepatitis and hepatocellular carcinoma, identifying NEMO as a tumor suppressor in the liver.},
  author       = {Luedde, Tom and Beraza, Naiara and Kotsikoris, Vasileios and van Loo, Geert and Nenci, Arianna and De Vos, Rita and Roskams, Tania and Trautwein, Christian and Pasparakis, Manolis},
  issn         = {1535-6108},
  journal      = {CANCER CELL},
  keywords     = {INCONTINENTIA PIGMENTI,NF-KAPPA-B,DEFICIENT MICE,TNF-ALPHA,IKK-BETA,EMBRYONIC LETHALITY,KINASE IKK,APOPTOSIS,DEATH,DEGENERATION},
  language     = {eng},
  number       = {2},
  pages        = {119--132},
  title        = {Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma},
  url          = {http://dx.doi.org/10.1016/j.ccr.2006.12.016},
  volume       = {11},
  year         = {2007},
}

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