HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-κB pathway

被引：333

作者：

Zhou, BP ^{[1
]}

Hu, MCT ^{[1
]}

Miller, SA ^{[1
]}

Yu, ZM ^{[1
]}

Xia, WY ^{[1
]}

Lin, SY ^{[1
]}

Hung, MC ^{[1
]}

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Breast Canc Basic Res Program, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2000年 / 275卷 / 11期

关键词：

D O I：

10.1074/jbc.275.11.8027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Overexpression of HER-2/neu correlates with poor survival of breast and ovarian cancer patients and induces resistance to tumor necrosis factor (TNF), which causes cancer cells to escape from host immune defenses. The mechanism of HER-2/neu-induced TNF resistance is unknown. Here we report that HER-2/neu activates Akt and NF-KB without extracellular stimulation. Blocking of the Akt pathway by a dominant-negative Akt sensitizes the HER-2/neu-overexpressing cells to TNF-induced apoptosis and inhibites I kappa B kinases, I kappa B phosphorylation, and NF-KB activation. Our results suggested that HER-2/neu constitutively activates the Akt/NF-kappa B anti-apoptotic cascade to confer resistance to TNF on cancer cells and reduce host defenses against neoplasia.

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页码：8027 / 8031

页数：5

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