title: Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2.
abstract: Aberrant constitutive expression of c-Rel, p65 and p50 NF-kappaB subunits has been reported in over 90% of breast cancers. Recently, we characterized a de novo RelB NF-kappaB subunit synthesis pathway, induced by the cytomegalovirus (CMV) IE1 protein, in which binding of p50-p65 NF-kappaB and c-Jun-Fra-2 AP-1 complexes to the RELB promoter work in synergy to potently activate transcription. Although RelB complexes were observed in mouse mammary tumours induced by either ectopic c-Rel expression or carcinogen exposure, 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 (ERalpha)-negative breast cancer cells. ERalpha signalling reduced levels of functional NF-kappaB and Fra-2 AP-1 and inhibited de novo RelB synthesis, leading to an inverse correlation between RELB and ERalpha gene expression in human breast cancer tissues and cell lines. Induction of Bcl-2 by RelB promoted the more invasive phenotype of ERalpha-negative cancer cells. Thus, inhibition of de novo RelB synthesis represents a new mechanism whereby ERalpha controls epithelial to mesenchymal transition (EMT).
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors: Xiaobo
authors: X
authors: Wang
authors: Karine
authors: K
authors: Belguise
authors: Nathalie
authors: N
authors: Kersual
authors: Kathrin H
authors: KH
authors: Kirsch
authors: Nora D
authors: ND
authors: Mineva
authors: Florence
authors: F
authors: Galtier
authors: Dany
authors: D
authors: Chalbos
authors: Gail E
authors: GE
authors: Sonenshein
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D051921:Fos-Related Antigen-2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051841:Transcription Factor RelB / Q000235:genetics* / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D051921:Fos-Related Antigen-2; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051841:Transcription Factor RelB