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

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