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

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.