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

被引：40

作者：

Bado, Igor ^{[1
]}

Nikolos, Fotis ^{[1
]}

Rajapaksa, Gayani ^{[1
]}

Gustafsson, Jan-Ake ^{[1
]}

Thomas, Christoforos ^{[1
]}

机构：

[1] Univ Houston, Dept Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX 77204 USA

来源：

ONCOTARGET | 2016年 / 7卷 / 12期

关键词：

estrogen receptor beta; mutant p53; triple-negative breast cancer; cell invasion; p63; ESTROGEN-RECEPTOR-BETA; LI-FRAUMENI-SYNDROME; TUMOR-SUPPRESSOR; GENE-EXPRESSION; P63; METASTASIS; ER-BETA-1; ALPHA; MUTATIONS; REPRESSES;

D O I：

10.18632/oncotarget.7300

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：13599 / 13611

页数：13

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