Peroxisomal branched chain fatty acid beta-oxidation pathway is upregulated in prostate cancer

Abstract

Overexpression of alpha-methylacyl-CoA racemase (AMACR), an enzyme involved in branched chain fatty acid beta-oxidation, in prostate cancer has been reported. Here, we report that an enzyme downstream from AMACR in the peroxisomal branched chain fatty acid beta-oxidation pathway-D-bifunctional protein (DBP)-is also upregulated in prostate cancer at both mRNA and protein levels, accompanied by increased enzymatic activity. Furthermore, our data suggest that pristanoyl-CoA oxidase (ACOX3), which is expressed at extremely low level in other human organs studied including the liver, might contribute significantly to peroxisomal branched chain fatty acid beta-oxidation in human prostate tissue and some prostate cancer cell lines. In contrast to these results for peroxisomal enzymes, no significant expression changes of mitochondrial fatty acid beta-oxidation enzymes were observed in prostate cancer tissues through comprehensive quantitative RT-PCR screening. These data for the first time provide evidence for the selective over-activation of peroxisomal branched chain fatty acid beta-oxidation in prostate cancer, emphasizing a new metabolic change during prostate oncogenesis.