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Molecular and Cellular Biology, July 2009, p. 3832-3844, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.00032-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

RelB NF-B Represses Estrogen Receptor Expression via Induction of the Zinc Finger Protein Blimp1 ^,

Xiaobo Wang ,^1,, Karine Belguise,^1,,¶ Christine F. O'Neill,^1,|| Nuria Sánchez-Morgan,¹ Mathilde Romagnoli,¹ Sean F. Eddy,^1,# Nora D. Mineva,¹ Ziyang Yu,¹ Chengyin Min,¹ Vickery Trinkaus-Randall,² Dany Chalbos,³ and Gail E. Sonenshein^1*

Department of Biochemistry and Women's Health Interdisciplinary Research Center,¹ Departments of Ophthalmology and Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118,² INSERM, U896, Université Montpellier 1, CRLC Val d'Aurelle Paul Lamarque, Montpellier, France³

Received 8 January 2009/ Returned for modification 9 March 2009/ Accepted 30 April 2009

Aberrant constitutive expression of NF-B 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 (ER)-negative breast cancers versus ER-positive ones, due in part to repression of RelB synthesis by ER signaling. Notably, RelB promoted a more invasive phenotype in ER-negative cancers via induction of the BCL2 gene. We report here that RelB reciprocally inhibits ER 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 ER (ESR1) gene transcription. Commensurately higher Blimp1/PRDM1 expression was detected in ER-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-B subunit mediates repression, specifically of ER, thereby promoting a more migratory phenotype.

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* Corresponding author. Mailing address: Boston University School of Medicine, Department of Biochemistry K615, 72 E. Concord Street, Boston, MA 02118. Phone: (617) 638-4120. Fax: (617) 638-4252. E-mail: gsonensh{at}bu.edu

Published ahead of print on 11 May 2009.

Supplemental material for this article may be found at http://mcb.asm.org/.

X.W. and K.B. contributed equally to this study.

Present address: Department of Biological Chemistry, Center for Cell Dynamics, Johns Hopkins School of Medicine, 755 North Wolfe Street, Baltimore, MD 21205.

^¶ Present address: INSERM U896, IRCM, Parc Euromédecine-Val d'Aurelle, 34298 Montpellier, France.

^|| Present address: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074.

^# Present address: Genstruct, Inc., One Alewife Center, Cambridge, MA 02140.

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Molecular and Cellular Biology, July 2009, p. 3832-3844, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.00032-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.