ABERRANT NUCLEAR FACTOR-KAPPA-B REL EXPRESSION AND THE PATHOGENESIS OF BREAST-CANCER/

Expression of nuclear factor-kappa B (NF-kappa B)/Rel transcription fa ctors has recently been found to promote cell survival, inhibiting the induction of apoptosis, In most cells other than B lymphocytes, NF-ka ppa B/Rel is inactive, sequestered in the cytoplasm, For example, nucl ear extracts from two human untransformed breast epithelial cell lines expressed only very low levels of NF-kappa B, Unexpectedly, nuclear e xtracts from two human breast tumor cell lines displayed significant l evels of NF-kappa B/Rel, Direct inhibition of this NF-kappa B/Rel acti vity in breast cancer cells induced apoptosis, High levels of NF-kappa B/Rel binding were also observed in carcinogen-induced primary rat ma mmary tumors, whereas only expectedly low levels were seen in normal r at 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 bre ast cancer, Given the role of NF-kappa B/Rel factors in cell survival, this aberrant activity may play a role in tumor progression, and repr esents a possible therapeutic target in the treatment of these tumors.