Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.
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.
Sovak
M A
MA
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Bellas
R E
RE
Kim
D W
DW
Zanieski
G J
GJ
Rogers
A E
AE
Traish
A M
AM
Sonenshein
G E
GE
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens; D002467:Cell Nucleus / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000494:pharmacology; D020569:Proto-Oncogene Proteins c-rel; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; C497593:RELB protein, human; D011993:Recombinant Fusion Proteins; C497595:Relb protein, rat; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB; D015127:9,10-Dimethyl-1,2-benzanthracene