Send to

Choose Destination
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

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


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.


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

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center