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Peroxisome proliferator-activated receptor gamma overexpression and knockdown: impact on human B cell lymphoma proliferation and survival

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Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifunctional transcription factor that regulates adipogenesis, immunity and inflammation. Our laboratory previously demonstrated that PPARγ ligands induce apoptosis in malignant B cells. While malignant B lineage cells such as B cell lymphoma express PPARγ, its physiological function remains unknown. Herein, we demonstrate that silencing PPARγ expression by RNAi in human Burkitt’s type B lymphoma cells increased basal and mitogen-induced proliferation and survival, which was accompanied by enhanced NF-κB activity and increased expression of Bcl-2. These cells also had increased survival upon exposure to PPARγ ligands and exhibited a less differentiated phenotype. In contrast, PPARγ overexpression in B lymphoma cells inhibited cell growth and decreased their proliferative response to mitogenic stimuli. These cells were also more sensitive to PPARγ-ligand induced growth arrest and displayed a more differentiated phenotype. Collectively, these findings support a regulatory role for PPARγ in the proliferation, survival and differentiation of malignant B cells. These findings further suggest the potential of PPARγ as a therapeutic target for B cell malignancy.

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Acknowledgments

This study was supported by DE11390, ES01247, a Hematology Training Grant NHLBI- T32HL007152, a Leukemia and Lymphoma Society Translational Research Award and a Lymphoma Research Foundation Award. Carolyn J. Baglole was supported by a Parker B. Francis Fellowship.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Tatiana M. Garcia-Bates, Scott A. Peslak, Sanjay B. Maggirwar & Richard P. Phipps

  2. Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, 850, Rochester, NY, 14642, USA

    Carolyn J. Baglole & Richard P. Phipps

  3. Lung Biology and Disease Program, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Carolyn J. Baglole & Richard P. Phipps

  4. The Lymphoma Biology Program of the James P. Wilmot Cancer Center, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Steven H. Bernstein

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  1. Tatiana M. Garcia-Bates
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  2. Scott A. Peslak
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  3. Carolyn J. Baglole
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  4. Sanjay B. Maggirwar
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  6. Richard P. Phipps
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Correspondence to Richard P. Phipps.

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Garcia-Bates, T.M., Peslak, S.A., Baglole, C.J. et al. Peroxisome proliferator-activated receptor gamma overexpression and knockdown: impact on human B cell lymphoma proliferation and survival. Cancer Immunol Immunother 58, 1071–1083 (2009). https://doi.org/10.1007/s00262-008-0625-z

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  • DOI: https://doi.org/10.1007/s00262-008-0625-z

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