title: Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism.
abstract: Environmental chemicals with estrogenic activity, known as xenoestrogens, may cause impaired reproductive development and endocrine-related cancers in humans by disrupting endocrine functions. Aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) is believed to play important roles in a variety of physiological processes, including estrogen signaling pathways, that may be involved in the pathogenesis and therapeutic responses of endocrine-related cancers. However, much of the underlying mechanism remains unknown. In this study, we investigated whether ARNT2 expression is regulated by a range of representative xenoestrogens in human cancer cell lines. Bisphenol A (BPA), benzyl butyl phthalate (BBP), and 1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) were found to be estrogenic toward BG1Luc4E2 cells by an E-CALUX bioassay. ARNT2 expression was downregulated by BPA, BBP, and o,p'-DDT in a dose-dependent manner in estrogen receptor 1 (ESR1)-positive MCF-7 and BG1Luc4E2 cells, but not in estrogen receptor-negative LNCaP cells. The reduction in ARNT2 expression in cells treated with the xenoestrogens was fully recovered by the addition of a specific ESR1 antagonist, MPP. In conclusion, we have shown for the first time that ARNT2 expression is modulated by xenoestrogens by an ESR1-dependent mechanism in MCF-7 breast cancer cells.
authors.affiliation: Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Japan.
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Qin
authors.forename: Hiroko
authors.initials: H
authors.lastname: Zaha
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagano
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshinaga
authors.forename: Junzo
authors.initials: J
authors.lastname: Yonemoto
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D003634:DDT / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009994:Osmolar Concentration; D010051:Ovarian Neoplasms / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010795:Phthalic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D015262:Xenobiotics / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D001559:Benzhydryl Compounds; D003634:DDT; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D009363:Neoplasm Proteins; D010636:Phenols; D010795:Phthalic Acids; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D015262:Xenobiotics; C524478:1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole; C490989:ARNT2 protein, human; C506487:ESR1 protein, human; C016340:o,p'-DDT; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C027561:butylbenzyl phthalate