Er Beta Decreases The Invasiveness Of Triple-Negative Breast Cancer Cells By Regulating Mutant P53 Gain-Of-Function

Triple-negative breast cancers (TNBCs) display distinct metastatic potential and a poor prognosis despite a relative chemosensitivity. Most (80%) of these highly aggressive tumors express mutant p53 proteins that are known to elicit oncogenic activities that contribute to metastasis and chemoresistance. Despite the lack of estrogen receptor α (ERα), TNBCs express wild-type ERβ (ERβ1). We previously showed that ERβ1 impedes epithelial to mesenchymal transition (EMT) in TNBC cells by repressing epidermal growth factor receptor (EGFR) signaling. Our recent findings indicate that ERβ1 regulates EGFR expression and decreases the invasiveness of TNBC cells by interacting with mutant p53 and inhibiting its function. Suppression of a mutant p53 transcriptional program and induction of p63 activity are essential for the anti-migratory activity of ERβ1 in TNBC cells. These results describe an ERβ1/mutant p53 interaction that disturbs oncogenic signals to inhibit aggressiveness in TNBC. Citation Format: Igor Bado, Fotis Nikolos, Gayani Rajapaksa, Jan-Ake Gustafsson, Christoforos Thomas. ERβ decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 gain-of-function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5043. doi:10.1158/1538-7445.AM2015-5043