TY - JOUR
T1 - HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF- κB pathway
AU - Zhou, Binhua P.
AU - Hu, Mickey C.T.
AU - Miller, Stephanie A.
AU - Yu, Zhenming
AU - Xia, Weiya
AU - Lin, Shiaw Yih
AU - Hung, Mien Chie
PY - 2000/3/17
Y1 - 2000/3/17
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.275.11.8027
DO - 10.1074/jbc.275.11.8027
M3 - Article
C2 - 10713122
AN - SCOPUS:0034677776
SN - 0021-9258
VL - 275
SP - 8027
EP - 8031
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 11
ER -
