Involvement of Fatty Acid Binding Protein 5 and PPARβδ in Prostate Cancer Cell Growth

Abstract EN

Fatty acid binding protein 5 (FABP5) delivers ligands from the cytosol directly to the nuclear receptor PPARβ/δ and thus facilitates the ligation and enhances the transcriptional activity of the receptor.

We show here that expression levels of both FABP5 and PPARβ/δ are correlated with the tumorigenic potential of prostate cancer cell lines.

We show further that FABP5 comprises a direct target gene for PPARβ/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/PPARβ/δ pathway induces PPARβ/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 PPARβ/δ inhibits the growth of the highly malignant prostate cancer PC3M cells.

These studies suggest that the FABP5/PPARβ/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.