The antiproliferative effects of PPARγ ligands in normal human mammary epithelial cells

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor in the steroid nuclear receptor super-family. Ligand activation of PPARgamma is associated with differentiation and an inhibition of proliferation in normal and malignant cells, including adipocytes, monocytes, and tumor cells in colon, prostate, and breast cancers. The current studies were undertaken to assess both the expression and functional activity of PPARgamma in cultured normal human mammary epithelial cells (HMECs) and tissue samples. Analyses by northern hybridization, immunoblotting, and immunohistochemistry demonstrate PPARgamma gene expression in HMECs and breast tissue specimens. DNA binding and transactivation assays indicate the presence of functionally active PPARgamma in HMECs. Treatment with PPARgamma selective ligands, 15-deoxy-Delta-(12,14)-prostaglandin J2 (15dPGJ2) and ciglitazone, inhibits the growth of HMECs in a dose-dependent manner. This growth inhibition is associated with alterations in cell cycle progression and the induction of apoptosis.