RelB NF-κB Represses Estrogen Receptor α Expression via Induction of the Zinc Finger Protein Blimp1
AbstractRelB NF-κB Represses Estrogen Receptor α 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 , * 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 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.