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

Igor Bado, Fotis Nikolos, Gayani Rajapaksa, Jan Åke Gustafsson, Christoforos Thomas

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13599-13611
Number of pages13
JournalOncotarget
Volume7
Issue number12
DOIs
StatePublished - Mar 22 2016

Keywords

  • Cell invasion
  • Estrogen receptor β
  • Mutant p53
  • P63
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology

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