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Expression of PPARgamma and its ligand-dependent growth inhibition in human brain tumor cell lines
Mihoko Kato1, Takashi Nagaya, Miyuki Fujieda
1Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601.
Abstract:
Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a superfamily of thyroid / steroid hormone receptors and regulates transcription of their target genes in a ligand-dependent manner. Recently, PPARgamma was reported to be expressed in several cell lines derived from breast, colon, stomach and lung cancers. Activation of PPARgamma by its ligand inhibits the growth of these tumor cells, suggesting that PPARgamma ligand is a potential anti-cancer agent in PPARgamma-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 PPARgamma mRNA. The results prompted us to study whether PPARgamma 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 PPARgamma ligands, troglitazone, induced growth inhibition in both cell lines. Further analyses revealed that this growth inhibition is caused by a PPARgamma-mediated induction of apoptosis. These results suggest that PPARgamma ligands could be a potential therapeutic agent for the treatment of the brain tumors expressing this receptor.
Insights
Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in most gliomas. Its ligand, troglitazone, inhibits brain tumor cell growth by inducing apoptosis, suggesting potential as a novel anti-cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor regulating gene transcription.
- PPARgamma is expressed in various cancer cells, and its activation inhibits tumor growth.
- PPARgamma expression and function in brain tumors remain largely uninvestigated.
Purpose of the Study:
- To investigate PPARgamma expression in human glioma tissues and cell lines.
- To determine the effect of PPARgamma ligands on brain tumor cell growth.
- To elucidate the mechanism underlying PPARgamma ligand-mediated growth inhibition.
Main Methods:
- Quantitative analysis of PPARgamma mRNA expression in 20 glioma patient samples.
- Assessment of PPARgamma expression in 9 brain tumor cell lines (glioma and neuroblastoma).
- Treatment of cell lines with troglitazone (a PPARgamma ligand) and evaluation of cell growth and apoptosis.
Main Results:
- PPARgamma mRNA was detected in 95% of the analyzed glioma tissues.
- PPARgamma was expressed in a glioma cell line (SK-MG-1) and a neuroblastoma cell line (NB-1).
- Troglitazone significantly inhibited the growth of SK-MG-1 and NB-1 cells by inducing apoptosis.
Conclusions:
- PPARgamma is widely expressed in gliomas, indicating its potential relevance in brain tumor biology.
- PPARgamma ligands demonstrate anti-proliferative effects on brain tumor cell lines.
- PPARgamma ligands represent a promising therapeutic strategy for brain tumors expressing the receptor.
