Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2

被引：67

作者：

Shan, Changliang ^{[1
]}

Xu, Fuqing ^{[1
]}

Zhang, Shuai ^{[1
]}

You, Jiacong ^{[2
]}

You, Xiaona ^{[1
]}

Qiu, Liyan ^{[1
]}

Zheng, Jie ^{[2
]}

Ye, Lihong ^{[2
]}

Zhang, Xiaodong ^{[1
]}

机构：

[1] Nankai Univ, Coll Life Sci, Dept Canc Res,Inst Mol Biol, Key Lab Mol Microbiol & Technol,Minist Educ, Tianjin 300071, Peoples R China

[2] Nankai Univ, Coll Life Sci, Minist Educ, Dept Biochem,Key Lab Bioact Mat, Tianjin 300071, Peoples R China

来源：

CELL RESEARCH | 2010年 / 20卷 / 05期

关键词：

hepatitis B virus X protein; proliferation; signal pathway; arachidonic acid metabolites; ERK; HEPATOCELLULAR-CARCINOMA; ACTIVATOR PROTEIN-1; HEPATOMA-CELLS; AKT ACTIVATION; UP-REGULATION; DNA-REPAIR; P38; MAPK; EXPRESSION; CYCLOOXYGENASE-2; APOPTOSIS;

D O I：

10.1038/cr.2010.49

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.

引用

页码：563 / 575

页数：13

共 53 条

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