Disruption of PPARgamma signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy.

ABSTRACT: Peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Conditional prostatic epithelial knockout of PPARgamma in mice resulted in focal hyperplasia which developed into mouse prostatic intraepithelial neoplasia (mPIN). The grade of PIN became more severe with time. Electron microscopy (EM) showed accumulated secondary lysosomes containing cellular organelles and debris suggestive of autophagy. Consistent with this analysis the autophagy marker LC-3 was found to be upregulated in areas of PIN in PPARgamma KO tissues. We selectively knocked down PPARgamma2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histo

SUBMITTER: Jiang M 

PROVIDER: S-EPMC2821953 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature