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

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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
StatePublished - Dec 15 1997

Fingerprint

Breast Neoplasms
Cell Survival
Apoptosis
Human Mammary Glands
Tumor Cell Line
Carcinogens
Neoplasms
Cytoplasm
Breast
B-Lymphocytes
Transcription Factors
Epithelial Cells
Cell Line
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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.

Aberrant nuclear factor-κb/Rel expression and the pathogenesis of breast cancer. / Sovak, Mika A.; Bellas, Robert E.; Kim, Dong W.; Zanieski, Gregory J.; Rogers, Adrianne E.; Traish, Abdulmaged M.; Sonenshein, Gail E.

In: Journal of Clinical Investigation, Vol. 100, No. 12, 15.12.1997, p. 2952-2960.

Research output: Contribution to journalArticle

Sovak, MA, Bellas, RE, Kim, DW, Zanieski, GJ, Rogers, AE, Traish, AM & Sonenshein, GE 1997, 'Aberrant nuclear factor-κb/Rel expression and the pathogenesis of breast cancer', Journal of Clinical Investigation, vol. 100, no. 12, pp. 2952-2960.
Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM et al. Aberrant nuclear factor-κb/Rel expression and the pathogenesis of breast cancer. Journal of Clinical Investigation. 1997 Dec 15;100(12):2952-2960.
Sovak, Mika A. ; Bellas, Robert E. ; Kim, Dong W. ; Zanieski, Gregory J. ; Rogers, Adrianne E. ; Traish, Abdulmaged M. ; Sonenshein, Gail E. / Aberrant nuclear factor-κb/Rel expression and the pathogenesis of breast cancer. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 12. pp. 2952-2960.
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