Aberrant nuclear factor-κb/Rel expression and the pathogenesis of breast cancer

Mika A. Sovak, Robert E. Bellas, Dong W. Kim, Gregory J. Zanieski, Adrianne E. Rogers, Abdulmaged M. Traish, Gail E. Sonenshein

Research output: Contribution to journalArticle

611 Scopus citations

Abstract

Expression of nuclear factor-κB (NF-κB)/Rel transcription factors has recently been found to promote cell survival, inhibiting the induction of apoptosis. In most cells other than B lymphocytes, NF-κB/Rel is inactive, sequestered in the cytoplasm. For example, nuclear extracts from two human untransformed breast epithelial cell lines expressed only very low levels of NF-κB. Unexpectedly, nuclear extracts from two human breast tumor cell lines displayed significant levels of NF-κB/Rel. Direct inhibition of this NF- κB/Rel activity in breast cancer cells induced apoptosis. High levels of NF- κB/Rel binding were also observed in carcinogen-induced primary rat mammary tumors, whereas only expectedly low levels were seen in normal rat mammary glands. Furthermore, multiple human breast cancer specimens contained significant levels of nuclear NF-κB/Rel subunits. Thus, aberrant nuclear expression of NF-κB/Rel is associated with breast cancer. Given the role of NF-κB/Rel factors in cell survival, this aberrant activity may play a role in tumor progression, and represents a possible therapeutic target in the treatment of these tumors.

Original languageEnglish (US)
Pages (from-to)2952-2960
Number of pages9
JournalJournal of Clinical Investigation
Volume100
Issue number12
DOIs
StatePublished - Dec 15 1997

Keywords

  • 7,12-dimethylbeaz(α)anthracene
  • Apoptosis
  • Aromatic hydrocarbons
  • Rat model
  • Transcription factors

ASJC Scopus subject areas

  • Medicine(all)

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    Sovak, M. A., Bellas, R. E., Kim, D. W., Zanieski, G. J., Rogers, A. E., Traish, A. M., & Sonenshein, G. E. (1997). Aberrant nuclear factor-κb/Rel expression and the pathogenesis of breast cancer. Journal of Clinical Investigation, 100(12), 2952-2960. https://doi.org/10.1172/JCI119848