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  • Print publication year: 2013
  • Online publication date: February 2015

33 - Emerging roles of peroxisome proliferator-activated receptor gamma in cancer

from Part 2.3 - Molecular pathways underlying carcinogenesis: nuclear receptors
    • By Chenguang Wang, Department of Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center, Thomas Jeferson University, Philadelphia, PA, USA, Xuemin Zhang, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China, Lifeng Tian, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jeferson University, Philadelphia, PA, USA, Richard G. Pestell, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jeferson University, Philadelphia, PA, USA
  • Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
  • Publisher: Cambridge University Press
  • DOI: https://doi.org/10.1017/CBO9781139046947.034
  • pp 392-402

Summary

Focus

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors, which include PPARα, PPARγ, and PPARδ (1). PPARγ was initially cloned as a transcription factor involved in adipocyte differentiation. Subsequent studies suggested a broad spectrum of PPARγ functions in lipid metabolism, inflammation, atherogenesis, and cell differentiation, as well as in tumorigenesis. Herein, we review recent studies suggesting a dominant role for PPARγ in processes related to cancer initiation and progression, and describe the mechanisms by which PPARγ regulates cell-cycle progression, cell death, and angiogenesis.

Structural features of PPARγ

There are three PPARγ isoforms (γ1, γ2, and γ3). Both PPARγ1 and PPARγ2 are abundantly expressed in adipose tissue, whereas PPARγ1 expression is detected in liver, spleen, heart tissues, and epithelium of a variety of tissues including breast and prostate. Their modular structure resembles other nuclear hormone receptors with an N-terminal activation function 1 (AF-1), a DNA-binding domain (DBD), and a C-terminal ligand-binding domain (activation function 2, AF-2).

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