Autophagy in nuclear receptor PPAR gamma-deficient mouse prostatic carcinogenesis

作者：Jiang Ming^*; Jerome W Gray; Hayward Simon W

来源：Autophagy, 2010, 6(1): 175-176.

• autophagy
• peroxisome proliferator-activated receptor (PPAR)gamma
• fatty acid oxidation
• oxidative stress
• differentiation
• prostatic intraepithelial neoplasia
• PIN

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) 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 PPAR gamma- and PPAR gamma 2-deficiency in mouse prostate epithelia. Autophagy accompanied the altered cellular proliferation and de-differentiation that resulted in PPAR gamma-/gamma 2-deficient mouse prostatic intraepithelial neoplasia (mPIN). Electron microscopy showed accumulated defective lysosomes and autophagic vacuoles in PPAR gamma-/gamma 2-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 PPAR gamma-null cells could be rescued by re-expression of either the PPAR gamma 1 or -gamma 2 isoform. Our paper examines the links between autophagy and PPAR gamma-related subcellular and histopathological changes taking place during murine prostatic carcinogenesis.

• 出版日期2010-1-1