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

Binhua P. Zhou, Mickey C.T. Hu, Stephanie A. Miller, Zhenming Yu, Weiya Xia, Shiaw Yih Lin, Mien Chie Hung

Research output: Contribution to journalArticlepeer-review

341 Scopus citations

Abstract

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-κB 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 IκB kinases, IκB phosphorylation, and NF-κB activation. Our results suggested that HER-2/neu constitutively activates the Akt/NF-κB anti-apoptotic cascade to confer resistance to TNF on cancer cells and reduce host defenses against neoplasia.

Original languageEnglish
Pages (from-to)8027-8031
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number11
DOIs
StatePublished - Mar 17 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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