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Role of aromatase activation on sodium arsenite-induced proliferation, migration, and invasion of MDA-MB-231 and MDA-MB-453 breast cancer cell lines.

Abstract：

:Arsenic is an endocrine disruptor that promotes breast cancer (BCa) development. Estrogen synthesis, through aromatase activation, is essential for BCa promotion and progression through activating the G-coupled estrogen receptor 1 (GPER1), regulating rapid nongenomic effects involved in cell proliferation and migration of BCa cells. Herein, was studied the role of aromatase activation and the GPER1 pathway on sodium arsenite-induced promotion and progression of MDA-MB-231 and MDA-MB-453 BCa cell lines. Our results demonstrated that 0.1 μM of sodium arsenite induces cell proliferation, migration, invasion, and stimulates aromatase activity of BCa cell lines MDA-MB-231, MDA-MB-453, MCF-7, but not in a nontumorigenic breast epithelial cell line (MCF-12A). Using letrozole (an aromatase inhibitor) and G-15 (a GPER1-selective antagonist), we demonstrated that sodium arsenite-induced proliferation and migration is mediated by induction of aromatase enzyme and, at least in part, by GPER1 activation in MDA-MB-231 and MDA-MB-453 cells. Sodium arsenite induced phosphorylation of Src that participated in sodium arsenite-induced aromatase activity, and -cell proliferation of MDA-MB-231 cell line. Overall, data suggests that sodium arsenite induces a positive-feedback loop, resulting in the promotion and progression of BCa cells, through induction of aromatase activity, E2 production, GPER1 stimulation, and Src activation.

journal_name

Toxicology

journal_title

Toxicology

authors

Reyes-Vázquez L,Hernández AJA,Calderón-Aranda ES

doi

10.1016/j.tox.2020.152440

subject

Has Abstract

pub_date

2020-05-15 00:00:00

pages

152440

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(20)30079-2

journal_volume

437

pub_type

杂志文章

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