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

作者：Mika A. Sovak, Robert E. Bellas, Dong Wook Kim, Gregory Zanieski, Adrianne E. Rogers, Abdulmaged M. Traish, Gail E Sonenshein · 发表于：Journal of Clinical Investigation · 年份：1997 · DOI：10.1172/jci119848 · 被引用次数：722 · 研究领域：NF-κB Signaling Pathways、Cytokine Signaling Pathways and Interactions、Retinoids in leukemia and cellular processes

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.