title: Autophagy in nuclear receptor PPARgamma-deficient mouse prostatic carcinogenesis.
abstract: Peroxisome proliferator-activated receptor-gamma (PPARgamma) 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 PPARgamma- and PPARgamma2-deficiency in mouse prostate epithelia. Autophagy accompanied the altered cellular proliferation and de-differentiation that resulted in PPARgamma-/gamma2-deficient mouse prostatic intraepithelial neoplasia (mPIN). Electron microscopy showed accumulated defective lysosomes and autophagic vacuoles in PPARgamma-/gamma2-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 PPARgamma-null cells could be rescued by re-expression of either the PPARgamma1 or -gamma2 isoform. Our paper examines the links between autophagy and PPARgamma-related subcellular and histopathological changes taking place during murine prostatic carcinogenesis.
authors.affiliation: Department of Urologic Surgery, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. ming.jiang.1@vanderbilt.edu
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: W Gray
authors.initials: WG
authors.lastname: Jerome
authors.forename: Simon W
authors.initials: SW
authors.lastname: Hayward
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology
chemical_list: D047495:PPAR gamma