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Environ Toxicol. 2016 Sep;31(9):1133-46. doi: 10.1002/tox.22122. Epub 2015 Mar 2.

Sodium arsenite inhibited genomic estrogen signaling but induced pERα (Ser118) via MAPK pathway in breast cancer cells.

Author information

1
Laboratory of Pharmacology, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Laksi, Bangkok, 10210, Thailand.
2
Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Laksi, Bangkok, 10210, Thailand.
3
Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education, Thailand.

Abstract

Arsenic (As) is considered a major environmental health threat worldwide due to its widespread contamination in drinking water. Recent studies reported that arsenic is a potential xenoestrogen as it interfered with the action of estrogen (E2) and estrogen receptor (ER) signaling. The present study investigated the effects of sodium arsenite (NaAsO2 ) on estrogen signaling in human breast cancer cells. The results demonstrated that NaAsO2 dose-dependently increased viability of hormone-dependent breast cancer MCF-7 and T47D cells expressing both ERα and ERβ but not hormone-independent MDA-MB-231 cells expressing ERβ. These suggested ERα contribution to NaAsO2 -stimulated breast cancer cells growth. NaAsO2 induced down-regulation of ERα but up-regulation of ERβ protein expressions in T47D cells. Moreover, NaAsO2 dose-dependently inhibited E2-induced ER transcriptional activity as it decreased E2-mediated ERE-luciferase transcription activation and PgR mRNA transcription but increased pS2 mRNA transcription. However, NaAsO2 induced both rapid and sustained activation of ERK1/2 and increased in phosphorylation of ERα at serine 118 residue, c-fos and c-myc protein expressions. These results indicated that NaAsO2 interferes the genomic estrogen-signaling pathway but induces activation of a rapid nongenomic signal transduction through ERK1/2 pathway which may contribute to its proliferative effect on hormone-dependent breast cancer cells.

KEYWORDS:

ERK1/2; arsenic; breast cancer; estrogen; pERα (Ser118)

PMID:
25728338
DOI:
10.1002/tox.22122
[Indexed for MEDLINE]

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