RelB NF-kappaB represses estrogen receptor alpha expression via induction of the zinc finger protein Blimp1.

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.
Mesh Terms:
Base Sequence, Breast Neoplasms, Cell Line, Tumor, Cell Movement, DNA Primers, Estrogen Receptor alpha, Female, Gene Expression, Genes, bcl-2, Humans, Neoplasms, Hormone-Dependent, Phenotype, Proto-Oncogene Proteins c-bcl-2, Repressor Proteins, Transcription Factor RelB, ras Proteins
Mol. Cell. Biol.
Date: Jul. 01, 2009
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