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

作者：Bado Igor; Nikolos Fotis; Rajapaksa Gayani; Gustafsson Jan Ake; Thomas Christoforos^*

来源：Oncotarget, 2016, 7(12): 13599-13611.

DOI：10.18632/oncotarget.7300

• estrogen receptor beta
• mutant p53
• triple-negative breast cancer
• cell invasion
• p63

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 ER beta (ER beta 1) impedes epithelial to mesenchymal transition (EMT) and decreases the invasiveness of TNBC cells. In the present study we searched for signaling pathways that ER beta 1 uses to inhibit EMT and invasion in TNBC cells. We show that ER beta 1 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 ER beta 1. Downregulation of p63 represses the epithelial phenotype of ER beta 1-expressing cells and alters the expression of mutant p53 target genes. These results describe a novel mechanism through which ER beta 1 can disturb oncogenic signals to inhibit aggressiveness in TNBCs.

• 出版日期2016-3-22