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. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1133-1146, 2016.
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.
Watanyoo
W
Nakareangrit
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.
Apinya
A
Thiantanawat
Laboratory of Pharmacology, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Laksi, Bangkok, 10210, Thailand.
Daranee
D
Visitnonthachai
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.
Piyajit
P
Watcharasit
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.
Jutamaad
J
Satayavivad
D018053:Arsenites / Q000633:toxicity*; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D017670:Sodium Compounds / Q000633:toxicity*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D018053:Arsenites; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C508861:PSEN2 protein, human; D053766:Presenilin-2; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
ERK1/2; arsenic; breast cancer; estrogen; pERα (Ser118)