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

被引：512

作者：

Luedde, Tom

Beraza, Naiara

Kotsikoris, Vasileios

van Loo, Geert

Nenci, Arianna

De Vos, Rita

Roskams, Tania

Trautwein, Christian

Pasparakis, Manolis

机构：

[1] Univ Cologne, Inst Genet, D-50674 Cologne, Germany

[2] EMBL, Mouse Biol Unit, I-00016 Monterotondo, Rome, Italy

[3] Univ Hosp, Rhein Westfal TH Aachen, Med Clin 3, D-52074 Aachen, Germany

[4] Catholic Univ Louvain, Dept Pathol, B-3000 Louvain, Belgium

来源：

CANCER CELL | 2007年 / 11卷 / 02期

关键词：

D O I：

10.1016/j.ccr.2006.12.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The 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.

引用

页码：119 / 132

页数：14

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