RelB NF-κB Represses Estrogen Receptor α Expression via Induction of the Zinc Finger Protein Blimp1
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Published:2009-07-15
Issue:14
Volume:29
Page:3832-3844
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ISSN:0270-7306
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Container-title:Molecular and Cellular Biology
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language:en
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Short-container-title:Mol Cell Biol
Author:
Wang Xiaobo1, Belguise Karine1, O'Neill Christine F.1, Sánchez-Morgan Nuria1, Romagnoli Mathilde1, Eddy Sean F.1, Mineva Nora D.1, Yu Ziyang1, Min Chengyin1, Trinkaus-Randall Vickery2, Chalbos Dany3, Sonenshein Gail E.1
Affiliation:
1. Department of Biochemistry and Women's Health Interdisciplinary Research Center 2. Departments of Ophthalmology and Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 3. INSERM, U896, Université Montpellier 1, CRLC Val d'Aurelle Paul Lamarque, Montpellier, France
Abstract
ABSTRACT
Aberrant constitutive expression of NF-κB subunits, reported in more than 90% of breast cancers and multiple other malignancies, plays pivotal roles in tumorigenesis. Higher RelB subunit expression was demonstrated in estrogen receptor alpha (ERα)-negative breast cancers versus ERα-positive ones, due in part to repression of RelB synthesis by ERα signaling. Notably, RelB promoted a more invasive phenotype in ERα-negative cancers via induction of the
BCL2
gene. We report here that RelB reciprocally inhibits ERα synthesis in breast cancer cells, which contributes to a more migratory phenotype. Specifically, RelB is shown for the first time to induce expression of the zinc finger repressor protein Blimp1 (B-lymphocyte-induced maturation protein), the critical mediator of B- and T-cell development, which is transcribed from the
PRDM1
gene. Blimp1 protein repressed
ERα
(
ESR1
) gene transcription. Commensurately higher Blimp1/
PRDM1
expression was detected in ERα-negative breast cancer cells and primary breast tumors. Induction of
PRDM1
gene expression was mediated by interaction of Bcl-2, localized in the mitochondria, with Ras. Thus, the induction of Blimp1 represents a novel mechanism whereby the RelB NF-κB subunit mediates repression, specifically of ERα, thereby promoting a more migratory phenotype.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
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