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The Increased Expression of Peroxisome Proliferator-Activated Receptor-1 in Human Breast Cancer Is Mediated by Selective Promoter Usage

Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, Kentucky

Peroxisome proliferator-activated receptor-1 (PPAR1) is transactivated by a wide range of ligands in normal human mammary epithelial and breast cancer cells. Although transactivation of PPAR mediates the expression of genes that are markers of differentiation, its overexpression in cancers of the breast, thyroid, colon, and lung suggests its dysregulation may play a role in oncogenesis, cancer progression, or both. We report the overexpression of PPAR is caused by the use of a tumor-specific promoter in breast cancer cells that is distinct from the promoter used in normal epithelia. Thus, the increase in PPAR expression seen in breast cancer cells results from promoter recruitment, providing new insights into the expression and actions of PPAR in breast cancer.

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