TY - JOUR
T1 - Cyclooxygenase-2 promoter activation by the aromatic hydrocarbon receptor in breast cancer MCF-7 cells
T2 - Repressive effects of conjugated linoleic acid
AU - Degner, Stephanie C.
AU - Kemp, Michael Q.
AU - Hockings, Jennifer K.
AU - Romagnolo, Donato F.
N1 - Funding Information:
We thank Dr. McIntyre, University of Utah, Salt Lake City, and Dr. David S. Pasco, University of Mississippi, Oxford for providing, respectively, the expression vector p3.9COX-2 and pCYP1A1–4XRE. We gratefully acknowledge E. A. Mash (Southwest Environmental Health Sciences Core Facility, University of Arizona, Tucson, AZ) for synthesis of 3M4NF. TCDD has been supplied by the National Cancer Institute (NCI), Division of Cancer Biology, Chemical and Physical Carcinogenesis Branch and distributed by Midwest Research Institute under a contract to NCI (64 CFR 72090, 64 CFR 28205). This work was supported in part by fellowships from Graduate Training Program T32 ES-07091-24 (J. K. Hockings and S. C. Degner) and a grant (100116) from the Arizona Biomedical Research Commission (D. F. Romagnolo). S. C. Degner and M. Q. Kemp contributed equally to the manuscript. Address correspondence to Donato F. Romagnolo, Laboratory of Mammary Gland Biology, Department of Nutritional Sciences, 1177 East 4th Street, The University of Arizona, Tucson, AZ 85721-0038. Phone: 520-626-9108. FAX: 520-621-9446. E-mail: [email protected].
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
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U2 - 10.1080/01635580701485585
DO - 10.1080/01635580701485585
M3 - Article
C2 - 18001219
AN - SCOPUS:36849009763
SN - 0163-5581
VL - 59
SP - 248
EP - 257
JO - Nutrition and cancer
JF - Nutrition and cancer
IS - 2
ER -