Estrogen receptor beta increases sensitivity to enzalutamide in androgen receptor-positive triple-negative breast cancer.

Journal of Cancer Research and Clinical Oncology
Aristomenis AnestisMichalis V Karamouzis

Abstract

Androgen receptor (AR) is playing an important role in the progression of a subset of TNBC. We evaluated the impact of ERβ expression along with anti-AR drugs in AR-positive TNBC. ERβ expression was examined in AR-positive TNBC cell line using MTT assay, scratch and Annexin V-FITC assay in the presence or absence of anti-androgens. Protein levels of involved molecules were assessed using Western blot. Receptors' localization was detected by immunofluorescence and their physical association was examined using proximity ligation assay (PLA), which enables the visualization of interacting proteins in fixed cells and tissues. Transient transfection of ERβ in MDA-MB 453 AR-positive TNBC cell line significantly inhibited cell proliferation, metastatic potential and induced apoptosis. ERβ expression reversed the aggravating role of AR in both indirect and direct ways. Indirectly, ERβ decreased AR activation through the inhibition of PI3K/AKT signaling pathway. Directly, ERβ formed heterodimers with AR in MDA-MB 453 cells and in human tissue samples impeding AR from forming homodimers. Enzalutamide is a more potent anti-androgen in AR + TNBC compared to bicalutamide. ERβ expression increased the sensitivity of MDA-MB 453 cells to anti-...Continue Reading

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Citations

Jan 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aristomenis AnestisMichalis V Karamouzis
Mar 3, 2020·Journal of Biomolecular Structure & Dynamics·Arittra BhattacharjeeChaman Ara Keya
Sep 29, 2020·Frontiers in Endocrinology·Mengyao ChenFuming Qiu
Mar 27, 2020·OncoTargets and Therapy·Yanfang LiuJing Yao
Jun 11, 2020·Cancers·Assunta SellittoFrancesca Rizzo
Sep 19, 2020·Biomarker Research·Yujing Zhou, Xingdang Liu
Jan 21, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lei PengGuoxin Zhang
Oct 17, 2020·NPJ Breast Cancer·Anna R MichmerhuizenCorey W Speers
Jan 23, 2022·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Di ChenChengyu Luo

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