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

Abstract

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-kB 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. © 2009 Japanese Cancer Association.