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: Xian-Yang Qin, Hiroko Zaha, Reiko Nagano, Jun Yoshinaga, Junzo Yonemoto, Hideko Sone
• Journal: Toxicology letters (Toxicol Lett) Vol. 206 Issue 2 Pg. 152-7 (Oct 10 2011) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 21771643 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole
• ARNT2 protein, human
• Basic Helix-Loop-Helix Transcription Factors
• Benzhydryl Compounds
• ESR1 protein, human
• Endocrine Disruptors
• Estrogen Receptor alpha
• Estrogens, Non-Steroidal
• Neoplasm Proteins
• Phenols
• Phthalic Acids
• Piperidines
• Pyrazoles
• RNA, Messenger
• Xenobiotics
• Aryl Hydrocarbon Receptor Nuclear Translocator
• DDT
• o,p'-DDT
• bisphenol A
• butylbenzyl phthalate

Topics

• Aryl Hydrocarbon Receptor Nuclear Translocator (genetics, metabolism)
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Benzhydryl Compounds
• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• DDT (pharmacology)
• Down-Regulation (drug effects)
• Endocrine Disruptors (pharmacology)
• Estrogen Receptor alpha (antagonists & inhibitors, genetics, metabolism)
• Estrogens, Non-Steroidal (pharmacology)
• Female
• Genes, Reporter (drug effects)
• Humans
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• Osmolar Concentration
• Ovarian Neoplasms (metabolism)
• Phenols (pharmacology)
• Phthalic Acids (pharmacology)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• RNA, Messenger (metabolism)
• Response Elements (drug effects)
• Xenobiotics (pharmacology)