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HER-2/neu Blocks Tumor Necrosis Factor-induced Apoptosis via the Akt/NF-κB Pathway
Open accessAbstract
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-kappaB 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 inhibits IkappaB kinases, IkappaB phosphorylation, and NF-kappaB activation. Our results suggested that HER-2/neu constitutively activates the Akt/NF-kappaB anti-apoptotic cascade to confer resistance to TNF on cancer cells and reduce host defenses against neoplasia.
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Cited by
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“…ErbB2-overexpressing cancer cells and Akt is inhibited after ErbB2 downregulation by trastuzumab, which is critical for tras-functions to dephosphorylate PIP 3 to PIP 2 , leading to Akt de-phosphorylation. tuzumab’s antitumor effect (Ignatoski et al., 2000; Yakes et al., 2002; Zhou et al., 2000).”
BackgroundZhou, B. P., Deng, J., Xia, W., Xu, J., Li, Y. M., Gunduz, M., & Hung, M.-C. (2004) · Nature Cell Biology · doi:10.1038/ncb1173 · Cited by 1,581
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Metadata
- Authors
- Zhou, B. P., Hu, M. C.-T., Miller, S. A., Yu, Z., Xia, W., Lin, S.-Y., & Hung, M.-C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 275
- Issue
- 11
- Pages
- 8027-8031
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2052512448
- Cited by
- 371
- References
- 0
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: HER-2/neu Blocks Tumor Necrosis Factor-induced Apoptosis via the Akt/NF-κB Pathway. https://app.cochat.ai/papers/10.1074/jbc.275.11.8027
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- Zhou, B. P., Hu, M. C.-T., Miller, S. A., Yu, Z., Xia, W., Lin, S.-Y., & Hung, M.-C. (2000). HER-2/neu Blocks Tumor Necrosis Factor-induced Apoptosis via the Akt/NF-κB Pathway. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.275.11.8027
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