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Autophagic Punctum

Autophagy in nuclear receptor PPARγ-deficient mouse prostatic carcinogenesis

Ming Jiang, Walter Gray Jerome and Simon W. Hayward

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a major modulator of cellular lipid metabolism and organelle differentiation. To understand whether autophagy is involved in the processes of dysregulated fatty acid oxidation and induced oxidative stress accompanying prostatic carcinogenesis, we characterized in vitro and in vivo models of PPARγ- and PPARγ2-deficiency in mouse prostate epithelia. Autophagy accompanied the altered cellular proliferation and de-differentiation that resulted in PPARγ-/γ2-deficient mouse prostatic intraepithelial neoplasia (mPIN). Electron microscopy showed accumulated defective lysosomes and autophagic vacuoles in PPARγ-/γ2-deficient cells, suggestive of autophagy. Gene expression profiling indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal, mitochondrial and lysosomal maturation, lipid oxidation and degradation. Further, the putative autophagic phenotypes of PPARγ-null cells could be rescued by re-expression of either the PPARγ1 or -γ2 isoform. Our paper examines the links between autophagy and PPARγ-related subcellular and histopathological changes taking place during murine prostatic carcinogenesis.

Punctum to: Jiang M, Fernandez S, Jerome WG, He Y, Yu X, Cai H, Boone B, Yi Y, Magnuson MA, Roy-Burman P, Matusik RJ, Shappell SB, Hayward SW. Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy. Cell Death Differ 2009; PMID: 19834493; DOI: 10.1038/cdd.2009.148.

Authors

Ming Jiang Corresponding author: ming.jiang.1@vanderbilt.edu

Department of Urologic Surgery; Vanderbilt-Ingram Comprehensive Cancer Center; Vanderbilt University Medical Center; Nashville, TN USA

Walter Gray Jerome

Department of Cancer Biology; Department of Pathology; Vanderbilt-Ingram Comprehensive Cancer Center; Vanderbilt University Medical Center; Nashville, TN USA

Simon W. Hayward Corresponding author: simon.hayward@vanderbilt.edu

Department of Urologic Surgery; Department of Cancer Biology; Vanderbilt-Ingram Comprehensive Cancer Center; Vanderbilt University Medical Center; Nashville, TN USA