Cyclooxygenase-2 Promoter Activation by the Aromatic Hydrocarbon Receptor in Breast Cancer MCF-7 Cells: Repressive Effects of Conjugated Linoleic Acid

The role of the aromatic hydrocarbon receptor (AhR) in transcriptional regulation of the human cyclooxygenase-2 (COX-2) gene remains elusive. We report that the AhR-ligands benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced transcription activity of COX-2 in breast cancer MCF-7 ce...

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Bibliographic Details
Published in:Nutrition and cancer 2007-01, Vol.59 (2), p.248-257
Main Authors: Degner, Stephanie C., Kemp, Michael Q., Hockings, Jennifer K., Romagnolo, Donato F.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Breast Neoplasms - enzymology
Cell Line, Tumor
Cyclooxygenase 2 - genetics
Cyclooxygenase 2 - metabolism
Enzyme Activation - drug effects
Epidemiology
Gene Expression Regulation, Neoplastic
Gynecology. Andrology. Obstetrics
Humans
Ligands
Linoleic Acids, Conjugated - pharmacology
Mammary gland diseases
Medical sciences
Other treatments
Polychlorinated Dibenzodioxins - analogs & derivatives
Polychlorinated Dibenzodioxins - toxicity
Receptors, Aryl Hydrocarbon - antagonists & inhibitors
Receptors, Aryl Hydrocarbon - metabolism
Signal Transduction
Transcription, Genetic
Treatment. General aspects
Tumors
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Summary:The role of the aromatic hydrocarbon receptor (AhR) in transcriptional regulation of the human cyclooxygenase-2 (COX-2) gene remains elusive. We report that the AhR-ligands benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced transcription activity of COX-2 in breast cancer MCF-7 cells. The TCDD-dependent activation of the COX-2 promoter was abrogated by mutation of 2 xenobiotic response elements (XREs) = CGTG). We found that TCDD stimulated the binding of the AhR to COX-2 and cytochrome P4501A1 (CYP1A1) oligonucleotides containing consensus XREs. Conversely, the cotreatment with TCDD plus a mixture of conjugated linoleic acid (CLA) or selected CLA isomers prevented (CLAmix = t10,c12-CLA > c9,t11-CLA) the induction of transcription from the COX-2 promoter. The TCDD-induced binding of the AhR to COX-2 and CYP1A1 oligonucleotides was repressed by cotreatment with CLA (t10,c12-CLA > c9,t11-CLA), and the AhR antagonists, 3-methoxy-4-naphthoflavone, and resveratrol. We conclude that the AhR may be a suitable target for prophylactic strategies that target COX-2 expression.
ISSN:0163-5581
1532-7914
DOI:10.1080/01635580701485585