Letter abstract
Nature Cell Biology 9, 470 - 478 (2007)
Published online: 18 March 2007 | doi:10.1038/ncb1559
There is an Addendum (May 2007) associated with this Letter.
Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2
Xiaobo Wang1, Karine Belguise1, Nathalie Kersual3, Kathrin H. Kirsch1, Nora D. Mineva2, Florence Galtier3, Dany Chalbos3 & Gail E. Sonenshein1
Aberrant constitutive expression of c-Rel, p65 and p50 NF-
B subunits has been reported in over 90% of breast cancers1, 2. Recently, we characterized a de novo RelB NF-B subunit synthesis pathway, induced by the cytomegalovirus (CMV) IE1 protein, in which binding of p50–p65 NF-B and c-Jun–Fra-2 AP-1 complexes to the RELB promoter work in synergy to potently activate transcription3. Although RelB complexes were observed in mouse mammary tumours induced by either ectopic c-Rel expression4 or carcinogen exposure5, little is known about RelB in human breast disease. Here, we demonstrate constitutive de novo RelB synthesis is selectively active in invasive oestrogen receptor alpha (ER
)-negative breast cancer cells. ER signalling reduced levels of functional NF-B and Fra-2 AP-1 and inhibited de novo RelB synthesis, leading to an inverse correlation between RELB and ER
gene expression in human breast cancer tissues and cell lines. Induction of Bcl-2 by RelB promoted the more invasive phenotype of ER-negative cancer cells. Thus, inhibition of de novo RelB synthesis represents a new mechanism whereby ER controls epithelial to mesenchymal transition (EMT).
- Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
- Department of Pathology and Laboratory Medicine and the Women's Health Interdisciplinary Research Center, Boston University School of Medicine, Boston, MA 02118, USA.
- Inserm, U540, Montpellier, F-34090 and Univ. Montpellier I, Montpellier, F-34000, France.
Correspondence to: Gail E. Sonenshein1 e-mail: gsonensh@bu.edu
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