Aberrant Nuclear factor-kappaB/Rel Expression and the Pathogenesis of Breast Cancer

J Clin Invest. 1997 Dec 15;100(12):2952-60. doi: 10.1172/JCI119848.

Abstract

Expression of nuclear factor-kappaB (NF-kappaB)/Rel transcription factors has recently been found to promote cell survival, inhibiting the induction of apoptosis. In most cells other than B lymphocytes, NF-kappaB/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-kappaB. Unexpectedly, nuclear extracts from two human breast tumor cell lines displayed significant levels of NF-kappaB/Rel. Direct inhibition of this NF-kappaB/ Rel activity in breast cancer cells induced apoptosis. High levels of NF-kappaB/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-kappaB/Rel subunits. Thus, aberrant nuclear expression of NF-kappaB/Rel is associated with breast cancer. Given the role of NF-kappaB/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Apoptosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinogens
  • Cell Nucleus / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / metabolism
  • NF-kappa B / biosynthesis*
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / pharmacology
  • Proto-Oncogene Proteins c-rel
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Transcription Factor RelA
  • Transcription Factor RelB
  • Transcription Factors*
  • Tumor Cells, Cultured

Substances

  • Carcinogens
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • RELB protein, human
  • Recombinant Fusion Proteins
  • Relb protein, rat
  • Transcription Factor RelA
  • Transcription Factors
  • Transcription Factor RelB
  • 9,10-Dimethyl-1,2-benzanthracene