Constitutive Activation of Nuclear factor-kappaB Is Preferentially Involved in the Proliferation of Basal-Like Subtype Breast Cancer Cell Lines

Cancer Sci. 2009 Sep;100(9):1668-74. doi: 10.1111/j.1349-7006.2009.01228.x. Epub 2009 May 28.

Abstract

Constitutive nuclear factor (NF)-kappaB 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-kappaB activation nor the molecular mechanisms leading to its constitutive activation have been clearly defined. Here, we quantitatively analyzed basal NF-kappaB activity in 35 human breast cancer cell lines and found that most of the cell lines with high constitutive NF-kappaB 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-kappaB activation by expression of IkappaBalpha super-repressor reduced proliferation of the basal-like subtype cell lines. Expression levels of mRNA encoding NF-kappaB-inducing kinase (NIK) were elevated in several breast cancer cell lines, and RNA interference-mediated knockdown of NIK reduced NF-kappaB activation in a subset of the basal-like subtype cell lines with upregulated NIK expression. Taken together, these results suggest that constitutive NF-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Cell Proliferation*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured

Substances

  • NF-kappa B
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase