Journal article
Aryl Hydrocarbon Receptor (AHR) Agonists Induce MicroRNA-335 Expression And Inhibit Lung Metastasis of Estrogen Receptor Negative Breast Cancer Cells
Molecular cancer therapeutics, Vol.11(1), pp.108-118
01/2012
DOI: 10.1158/1535-7163.MCT-11-0548
PMCID: PMC3256275
PMID: 22034498
Abstract
The aryl hydrocarbon receptor (AHR) was initially identified as a receptor that bound 2,3,7,8-tetrachlorodibenzo-
p
-dioxin (TCDD) and related environmental toxicants; however, there is increasing evidence that the AHR is an important new drug target for treating multiple diseases including breast cancer. Treatment of estrogen receptor (ER)-negative MDA-MB-231 and BT474 breast cancer cells with TCDD or the selective AHR modulator 6-methyl-1,3,-trichlorodibenzofuran (MCDF) inhibited breast cancer cell invasion in a Boyden chamber assay. These results were similar to those previously reported for the antimetastic microRNA-335 (miR-335). Both TCDD and MCDF induced miR-335 in MDA-MB-231 and BT474 cells and this was accompanied by downregulation of SOX4, a miR-335-regulated (inhibited) gene. The effects of TCDD and MCDF on miR-335 and SOX4 expression and interactions of miR-335 with the 3'-UTR target sequence in the SOX4 gene were all inhibited in cells transfected with an oligonucleotide (iAHR) that knocks down the AHR, thus confirming AHR-miR-335 interactions. MCDF (40 mg/kg/day) also inhibited lung metastasis of MDA-MB-231 cells in a tail vein injection model, demonstrating that the AHR is a potential new target for treating patients with ER-negative breast cancer, a disease where treatment options and their effectiveness are limited.
Details
- Title: Subtitle
- Aryl Hydrocarbon Receptor (AHR) Agonists Induce MicroRNA-335 Expression And Inhibit Lung Metastasis of Estrogen Receptor Negative Breast Cancer Cells
- Creators
- Shu Zhang - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030KyoungHyun Kim - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030Un Ho Jin - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030Catherine Pfent - Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843Huojun Cao - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030Brad Amendt - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030Xinyi Liu - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030Heather Wilson-Robles - Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX 77843Stephen Safe - Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030
- Resource Type
- Journal article
- Publication Details
- Molecular cancer therapeutics, Vol.11(1), pp.108-118
- DOI
- 10.1158/1535-7163.MCT-11-0548
- PMID
- 22034498
- PMCID
- PMC3256275
- NLM abbreviation
- Mol Cancer Ther
- ISSN
- 1535-7163
- eISSN
- 1538-8514
- Language
- English
- Date published
- 01/2012
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Endodontics; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984065720602771
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