Ma. Sovak et al., ABERRANT NUCLEAR FACTOR-KAPPA-B REL EXPRESSION AND THE PATHOGENESIS OF BREAST-CANCER/, The Journal of clinical investigation, 100(12), 1997, pp. 2952-2960
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.