NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: Potential involvement of ZEB-1 and ZEB-2

H. L. Chua, P. Bhat-Nakshatri, S. E. Clare, A. Morimiya, S. Badve, H. Nakshatri

Research output: Contribution to journalArticle

413 Scopus citations


The transcription factor nuclear factor kappa B (NF-κB) is constitutively active in both cancer cells and stromal cells of breast cancer; however, the precise role of activated NF-κB in cancer progression is not known. Using parental MCF10A cells and a variant that expresses the myoepithelial marker p63 stably overexpressing the constitutively active p65 subunit of NF-κB (MCF10A/p65), we show that NF-κB suppresses the expression of epithelial specific genes E-cadherin and desmoplakin and induces the expression of the mesenchymal specific gene vimentin. P65 also suppressed the expression of p63 and the putative breast epithelial progenitor marker cytokeratin 5/6. MCF10A/p65 cells were phenotypically similar to cells undergoing epithelial to mesenchymal transition (EMT). MCF10A/p65 cells failed to form characteristic acini in three-dimensional Matrigel. Analysis of parental and MCF10A/p65 cells for genes previously shown to be involved in EMT revealed elevated expression of ZEB-1 and ZEB-2 in MCF10A/p65 cells compared to parental cells. In transient transfection assays, p65 increased ZEB-1 promoter activity. Furthermore, MCF10A cells overexpressing ZEB-1 showed reduced E-cadherin and p63 expression and displayed an EMT phenotype. The siRNA against ZEB-1 or ZEB-2 reduced the number of viable MCF10A/p65 but not parental cells, suggesting the dependence of MCF10A/p65 cells to ZEB-1 and ZEB-2 for cell cycle progression or survival. MCF10A cells chronically exposed to tumor necrosis factor alpha (TNFα), a potent NF-κB inducer, also exhibited the EMT-like phenotype and ZEB-1/ZEB-2 induction, both of which were reversed following TNFα withdrawal.

Original languageEnglish (US)
Pages (from-to)711-724
Number of pages14
Issue number5
StatePublished - Feb 1 2007



  • Breast cancer
  • EMT
  • NF-κB
  • p63
  • ZEB-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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