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

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.