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This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: ERC-09-0054v1 16/3/835    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, S. Articles by Safe, S. PubMed PubMed Citation Articles by Zhang, S. Articles by Safe, S.

¹ Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 Holcombe Boulevard, Houston, Texas 77030, USA
² Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, Veterinary Research Building 410, College Station, Texas 77843-4466, USA
³ Dow Chemical Company, Toxicology and Environmental Research and Consulting, Midland, Michigan 48674, USA

(Correspondence should be addressed to S Safe, Department of Veterinary Physiology and Pharmacology, Texas A&M University; Email: ssafe{at}cvm.tamu.edu)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and the relatively non-toxic selective aryl hydrocarbon receptor (AhR) modulator 6-methyl-1,3,8-trichlorodibenzo-furan (MCDF) induced CYP1A1-dependent ethoxyresorufin O-deethylase activity and inhibited proliferation of seven estrogen receptor (ER) negative breast cancer cell lines. MCDF, TCDD and structurally related 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 3,3',4,4',5-pentachlorobiphenyl induced CYP1A1 and inhibited proliferation of BT-474 and MDA-MB-468 cells. In BT474 and MDA-MB-468 cells transfected with a small inhibitory RNA for the AhR, the antiproliferative activity of the chlorinated aromatic compounds was reversed, whereas for MCDF, only partial reversal was observed, suggesting that this compound acts through both AhR-dependent and AhR-independent pathways in these two cell lines. MCDF also inhibited tumor growth in athymic nude mice in which MDA-MB-468 cells were injected directly into the mammary fat pad. These results suggest that the AhR is a potential drug target for treatment of ER-negative breast cancer.