Expression of PPARgamma and its ligand-dependent growth inhibition in human brain tumor cell lines.

Abstract

Peroxisome proliferator‐activated receptor y (PPARγ) belongs to a superfamily of thyroid/steroid hormone receptors and regulates transcription of their target genes in a ligand‐dependent manner. Recently, PPARγ was reported to be expressed in several cell lines derived from breast, colon, stomach and lung cancers. Activation of PPARγ by its ligand inhibits the growth of these tumor cells, suggesting that PPARγ ligand is a potential anti‐cancer agent in PPARγ‐expressing tumors. However, its expression in brain tumors has not been studied. We thus studied the expression in glioma samples with different pathological stages from 20 patients. It was demonstrated that 95% of the glioma tissue expressed PPARγ mRNA. The results prompted us to study whether PPARγ ligand affects the growth of cell lines derived from brain tumors. The receptor expression was studied in 9 cell lines either derived from malignant glioma or neuroblastoma. The expression was detected in a glioma cell line SK‐MG‐1 and in a neuroblastoma cell line NB‐1. Addition of one of the PPARγ ligands, troglitazone, induced growth inhibition in both cell lines. Further analyses revealed that this growth inhibition is caused by a PPARγ‐mediated induction of apoptosis. These results suggest that PPARγ ligands could be a potential therapeutic agent for the treatment of the brain tumors expressing this receptor.