Peroxisomal branched chain fatty acid beta-oxidation pathway is upregulated in prostate cancer.
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.
Zha
Shan
S
Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ferdinandusse
Sacha
S
Hicks
Jessica L
JL
Denis
Simone
S
Dunn
Thomas A
TA
Wanders
Ronald J
RJ
Luo
Jun
J
De Marzo
Angelo M
AM
Isaacs
William B
WB
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004746:Enoyl-CoA Hydratase / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006836:Hydro-Lyases; D007150:Immunohistochemistry; D008113:Liver Neoplasms; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D064029:Peroxisomal Multifunctional Protein-2; D020675:Peroxisomes / Q000201:enzymology*; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D005227:Fatty Acids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D010088:Oxidoreductases; D015067:17-Hydroxysteroid Dehydrogenases; C066272:pristanoyl-CoA oxidase; D042962:Acyl-CoA Oxidase; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase