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Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2

Xiaobo Wang1, Karine Belguise, Nathalie Kersual

  • 1Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Nature Cell Biology
|March 21, 2007
PubMed

Insights

Constitutive de novo RelB synthesis is active in invasive estrogen receptor alpha-negative breast cancer cells. Estrogen receptor alpha signaling inhibits RelB synthesis, impacting cancer cell invasiveness and epithelial to mesenchymal transition.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Signaling

Background:

  • Aberrant expression of NF-kappaB subunits (c-Rel, p65, p50) is common in breast cancer.
  • A de novo RelB NF-kappaB subunit synthesis pathway, induced by cytomegalovirus (CMV) IE1 protein, involves NF-kappaB and AP-1 complexes activating RELB transcription.
  • RelB complexes are found in mouse mammary tumors, but their role in human breast cancer is poorly understood.

Purpose of the Study:

  • To investigate the role and regulation of de novo RelB synthesis in human breast cancer.
  • To determine the relationship between RelB expression and estrogen receptor alpha (ERalpha) signaling in breast cancer.
  • To elucidate the mechanism by which RelB influences breast cancer invasiveness and epithelial to mesenchymal transition (EMT).

Main Methods:

  • Analysis of RelB synthesis in invasive ERalpha-negative breast cancer cells.
  • Assessment of ERalpha signaling's impact on NF-kappaB and AP-1 activity.
  • Correlation analysis of RELB and ERalpha gene expression in human breast cancer tissues and cell lines.
  • Investigation of Bcl-2 induction by RelB and its effect on cancer cell phenotype.

Main Results:

  • Constitutive de novo RelB synthesis is selectively active in invasive ERalpha-negative breast cancer cells.
  • ERalpha signaling suppresses functional NF-kappaB and Fra-2 AP-1, inhibiting de novo RelB synthesis.
  • An inverse correlation exists between RELB and ERalpha gene expression in human breast cancer.
  • RelB-induced Bcl-2 expression promotes the invasive phenotype of ERalpha-negative cancer cells.

Conclusions:

  • De novo RelB synthesis is a key feature of invasive ERalpha-negative breast cancer.
  • ERalpha signaling acts as a negative regulator of de novo RelB synthesis, influencing breast cancer progression.
  • Inhibition of de novo RelB synthesis is a novel mechanism by which ERalpha controls EMT in breast cancer, offering potential therapeutic targets.

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