The Increased Expression of Peroxisome Proliferator-Activated Receptor-γ1 in Human Breast Cancer Is Mediated by Selective Promoter Usage

Abstract

Peroxisome proliferator-activated receptor-gamma1 (PPARgamma1) is transactivated by a wide range of ligands in normal human mammary epithelial and breast cancer cells. Although transactivation of PPARgamma 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 PPARgamma 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 PPARgamma expression seen in breast cancer cells results from promoter recruitment, providing new insights into the expression and actions of PPARgamma in breast cancer.