Involvement of fatty acid binding protein 5 and PPAR β/δ in prostate cancer cell growth

Abstract

Fatty acid binding protein 5 (FABP5) delivers ligands from the cytosol directly to the nuclear receptor PPAR β/ δ and thus facilitates the ligation and enhances the transcriptional activity of the receptor. We show here that expression levels of both FABP5 and PPAR β/ δ are correlated with the tumorigenic potential of prostate cancer cell lines. We show further that FABP5 comprises a direct target gene for PPAR β/ δ and thus the binding protein and its cognate receptor are engaged in a positive feedback loop. The observations demonstrate that, similarly to effects observed in mammary carcinomas, activation of the FABP5/PPAR β/ δ pathway induces PPAR β/ δ target genes involved in cell survival and growth and enhances cell proliferation and anchorage-independent growth in prostate cancer cells. Furthermore, the data show that downregulation of either FABP5 or PPAR β/ δ inhibits the growth of the highly malignant prostate cancer PC3M cells. These studies suggest that the FABP5/PPAR β/ δ pathway may play a general role in facilitating tumor progression and that inhibition of the pathway may comprise a novel strategy in treatment of cancer. Copyright © 2010 Elwin Morgan et al.