RelB NF-kappaB represses estrogen receptor alpha expression via induction of the zinc finger protein Blimp1.: RelB represses ERα transcription by inducing Blimp

Abstract : Aberrant constitutive expression of NF-kappaB 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 (ERalpha)-negative breast cancers versus ERalpha-positive ones, due in part to repression of RelB synthesis by ERalpha signaling. Notably, RelB promoted a more invasive phenotype in ERalpha-negative cancers via induction of the BCL2 gene. We report here that RelB reciprocally inhibits ERalpha 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 ERalpha (ESR1) gene transcription. Commensurately higher Blimp1/PRDM1 expression was detected in ERalpha-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-kappaB subunit mediates repression, specifically of ERalpha, thereby promoting a more migratory phenotype.
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Molecular and Cellular Biology, American Society for Microbiology, 2009, 29 (14), pp.3832-44. 〈10.1128/MCB.00032-09〉
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Xiaobo Wang, Karine Belguise, Christine F. O'Neill, Nuria Sánchez-Morgan, Mathilde Romagnoli, et al.. RelB NF-kappaB represses estrogen receptor alpha expression via induction of the zinc finger protein Blimp1.: RelB represses ERα transcription by inducing Blimp. Molecular and Cellular Biology, American Society for Microbiology, 2009, 29 (14), pp.3832-44. 〈10.1128/MCB.00032-09〉. 〈inserm-00396241〉

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