NF-κB inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen

L. A. deGraffenried, B. Chandrasekar, W. E. Friedrichs, E. Donzis, J. Silva, M. Hidalgo, J. W. Freeman, G. R. Weiss

Research output: Contribution to journalArticle

85 Scopus citations


Studies show that high Akt activity in breast carcinoma is associated with endocrine therapy resistance. Breast cancer cell lines expressing a constitutively active Akt are able to proliferate under reduced estrogen conditions, and are resistant to the growth inhibitory effects of tamoxifen. Understanding the targets of Akt signaling mediating tamoxifen resistance is of clinical significance. One possible target is nuclear factor kappa B (NF-κB), a transcription factor that plays a critical role in resistance to apoptosis and the induction of angiogenesis and invasion. In the present study, we found that Akt activity correlated with phosphorylation of IκB (the negative regulator of NF-κB), NF-κB DNA binding and tamoxifen resistance in vivo. Importantly, we found that co-treatment with the NF-κB inhibitor, parthenolide, or overexpression of IκB superrepressor restored tamoxifen sensitivity to our refractory Akt MCF-7 cells. These data suggest that activation of NF-κB via the PI3K/Akt signaling pathway may be a significant mechanism for development of endocrine therapy resistance in breast cancer, and that inhibition of NF-κB may be an effective treatment strategy to limit the progression of this disease.

Original languageEnglish (US)
Pages (from-to)885-890
Number of pages6
JournalAnnals of Oncology
Issue number6
StatePublished - Jun 1 2004



  • Akt
  • Breast cancer
  • NF-κB
  • Tamoxifen resistance

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

deGraffenried, L. A., Chandrasekar, B., Friedrichs, W. E., Donzis, E., Silva, J., Hidalgo, M., Freeman, J. W., & Weiss, G. R. (2004). NF-κB inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen. Annals of Oncology, 15(6), 885-890.