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The Antiproliferative Effects of PPARγ Ligands in Normal Human Mammary Epithelial Cells

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor in the steroid nuclear receptor superfamily. Ligand activation of PPARγ 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 PPARγ in cultured normal human mammary epithelial cells (HMECs) and tissue samples. Analyses by northern hybridization, immunoblotting, and immunohistochemistry demonstrate PPARγ gene expression in HMECs and breast tissue specimens. DNA binding and transactivation assays indicate the presence of functionally active PPARγ in HMECs. Treatment with PPARγ selective ligands, 15-deoxy-Δ-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.

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Authors and Affiliations

  1. Department of Surgery, The Ohio State University, Columbus, OH

    Lisa D. Yee, Yan Guo & Jamie Bradbury

  2. Department of Pathology, The Ohio State University, Columbus, OH

    Saul Suster

  3. Department of Medicine, The Ohio State University, Columbus, OH

    Steven K. Clinton

  4. Division of Medical Oncology, Duke University, Durham, NC, USA

    Victoria L. Seewaldt

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  1. Lisa D. Yee
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  6. Victoria L. Seewaldt
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Yee, L.D., Guo, Y., Bradbury, J. et al. The Antiproliferative Effects of PPARγ Ligands in Normal Human Mammary Epithelial Cells. Breast Cancer Res Treat 78, 179–192 (2003). https://doi.org/10.1023/A:1022978608125

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