Constitutive activation of nuclear factor‐κB is preferentially involved in the proliferation of basal‐like subtype breast cancer cell lines

Constitutive nuclear factor (NF)‐κB activation is thought to be involved in survival, invasion, and metastasis in various types of cancers. However, neither the subtypes of breast cancer cells with constitutive NF‐κB activation nor the molecular mechanisms leading to its constitutive activation have been clearly defined. Here, we quantitatively analyzed basal NF‐κB activity in 35 human breast cancer cell lines and found that most of the cell lines with high constitutive NF‐κB activation were categorized in the estrogen receptor negative, progesterone receptor negative, ERBB2 negative basal‐like subtype, which is the most malignant form of breast cancer. Inhibition of constitutive NF‐κB activation by expression of IκBα super‐repressor reduced proliferation of the basal‐like subtype cell lines. Expression levels of mRNA encoding NF‐κB‐inducing kinase (NIK) were elevated in several breast cancer cell lines, and RNA interference‐mediated knockdown of NIK reduced NF‐κB activation in a subset of the basal‐like subtype cell lines with upregulated NIK expression. Taken together, these results suggest that constitutive NF‐κB activation, partially dependent on NIK, is preferentially involved in proliferation of basal‐like subtype breast cancer cells and may be a useful therapeutic target for this subtype of cancer. (Cancer Sci 2009; 100: 1668–1674)