The Role of Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ) in the Human MCF7 Breast Cancer Cell Line

The role of PPARβ/δ in breast carcinogenesis remains unclear because some studies show that activating this receptor promotes breast cancer cell growth, while other studies show that activating this receptor inhibits breast cancer cell growth. Further, some studies suggest that the function of PPARβ/δ can be altered by the presence of fatty acid binding protein 5 (FABP5) and cell retinoic acid binding protein-II (CRABP-II) by diverting atRA or PPARβ/δ agonists to PPARβ/δ and promote cell proliferation by preventing activation of retinoic acid receptors (RARs). This study examined the effects of PPARβ/δ on cell proliferation in the presence of GW0742 (a PPARβ/δ agonist), GSK0660 (a PPARβ/δ antagonist) and all-trans retinoic acid (atRA a putative PPARβ/δ agonist) in a genetically engineered human MCF7 breast cancer cell line. Control cells (MCF7), cells infected with a control retrovirus (MCF7-MigR1), or cells infected with a retrovirus expressing PPARβ/δ (MCF7-MigR1 hPPAR) were treated with either atRA, GSK0660 and/or GW0742 and gene expression and cell proliferation were examined. This allowed for examining the hypothesis that the activity of PPARβ/δ can be altered by FABP5/CRABP-II ratio in a human breast cancer cell line. The mRNA levels of the PPARβ/δ target gene, adipose differentiation-related protein (ADRP) were increased by treatment with GW0742 but not by atRA. In contrast, atRA increased expression of the RAR target gene CYP26A but GW0742 had no effect on expression. While GSK0660 inhibited GW0742-induced ADRP mRNA, it had no effect on ADRP or CYP26A mRNA expression. The FABP5/CRABP-II ratio was measured by western blot analysis and relatively high. However, over-expression of PPARβ/δ did not influence the effect or lack of effect of GW0742 or atRA. Cell proliferation in response to GW0742, GSK0660 and atRA in MCF7 cells was not different between treatment