RRC ID 18591
著者 Qin XY, Zaha H, Nagano R, Yoshinaga J, Yonemoto J, Sone H.
タイトル Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism.
ジャーナル Toxicol Lett
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.
巻・号 206(2)
ページ 152-7
公開日 2011-10-10
DOI 10.1016/j.toxlet.2011.07.007
PII S0378-4274(11)01420-2
PMID 21771643
MeSH Aryl Hydrocarbon Receptor Nuclear Translocator / genetics Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism* Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Benzhydryl Compounds Breast Neoplasms / metabolism* Cell Line, Tumor DDT / pharmacology Down-Regulation / drug effects* Endocrine Disruptors / pharmacology* Estrogen Receptor alpha / antagonists & inhibitors Estrogen Receptor alpha / genetics Estrogen Receptor alpha / metabolism* Estrogens, Non-Steroidal / pharmacology* Female Genes, Reporter / drug effects Humans Neoplasm Proteins / antagonists & inhibitors Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Osmolar Concentration Ovarian Neoplasms / metabolism Phenols / pharmacology Phthalic Acids / pharmacology Piperidines / pharmacology Pyrazoles / pharmacology RNA, Messenger / metabolism Response Elements / drug effects Xenobiotics / pharmacology*
IF 3.569
引用数 16
WOS 分野 TOXICOLOGY
リソース情報
ヒト・動物細胞 MCF7(RCB1904) LNCap.FGC(RCB2144)