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Volume 12 Supplement 1

Breast Cancer Research 2010

Suppression of the NF-κB co-factor, Bcl3, delays the metastatic progression of breast cancer

A large proportion of breast cancers overexpress the HER receptors, HER1 or HER2. Generally these patients have a poor prognosis, exhibit resistance to first-line anti-cancer drugs, and frequently develop metastatic disease - the most common cause of patient death. NF-κB transcription factors lie downstream of HER1/2 signalling pathways and are aberrantly activated in the majority of these breast tumours.

We have found that a constitutive deficiency in Bcl3 (an NF-κB co-factor that modifies NF-κB signalling) delayed HER2 (ErbB2) tumour onset and inhibited metastasis of mammary tumours in mice while growth of primary tumours was unaffected. In those Bcl3-null animals that did acquire metastases, the size of secondary tumours was significantly reduced compared with controls. Critically, Bcl3 deficiency did not affect normal mammary function other than having a transitory effect on apoptosis of epithelial cells in the post-lactational mammary gland. Therefore, unlike other NF-κB regulators, Bcl3 exhibited tumour-specific effects in vivo. The pro-metastatic properties of Bcl3 were confirmed in several human breast cancer cell lines exhibiting elevated HER2 and/or HER1 levels, including aggressive basal-like tumour cell types.

These observations are significant because they suggest it may be possible to target Bcl3 in established tumour cells to reduce metastatic behaviour, and furthermore that Bcl3's effects are not restricted to ERBB2-positive breast tumours, consistent with the observed increase in NF-κB activity seen in both ERBB1-positive and ERBB2-positive breast tumours.

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Wakefield, A., Clarkson, R. Suppression of the NF-κB co-factor, Bcl3, delays the metastatic progression of breast cancer. Breast Cancer Res 12 (Suppl 1), P6 (2010).

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  • Breast Cancer
  • Breast Cancer Cell Line
  • Human Breast Cancer Cell
  • Human Breast Cancer Cell Line
  • Bcl3