ERβ decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function

// Igor Bado 1 , Fotis Nikolos 1 , Gayani Rajapaksa 1 , Jan-Åke Gustafsson 1 , Christoforos Thomas 1 1 Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas 77204, USA Correspondence to: Christoforos Thomas, e-mail: chthomas@uh.edu Keywords: estrogen receptor β, mutant p53, triple-negative breast cancer, cell invasion, p63 Received: November 05, 2015 Accepted: January 29, 2016 Published: February 10, 2016 ABSTRACT Most (80%) of the triple-negative breast cancers (TNBCs) express mutant p53 proteins that acquire oncogenic activities including promoting metastasis. We previously showed that wild-type ERβ (ERβ1) impedes epithelial to mesenchymal transition (EMT) and decreases the invasiveness of TNBC cells. In the present study we searched for signaling pathways that ERβ1 uses to inhibit EMT and invasion in TNBC cells. We show that ERβ1 binds to and opposes the transcriptional activity of mutant p53 at the promoters of genes that regulate metastasis. p63 that transcriptionally cooperates with mutant p53 also binds to ERβ1. Downregulation of p63 represses the epithelial phenotype of ERβ1-expressing cells and alters the expression of mutant p53 target genes. These results describe a novel mechanism through which ERβ1 can disturb oncogenic signals to inhibit aggressiveness in TNBCs.