title: Expression of PPARgamma and its ligand-dependent growth inhibition in human brain tumor cell lines.
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.
authors.affiliation: Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagaya
authors.forename: Miyuki
authors.initials: M
authors.lastname: Fujieda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Hisao
authors.initials: H
authors.lastname: Seo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002839:Chromans / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008024:Ligands; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D018076:DNA, Complementary; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D004247:DNA; D000077288:Troglitazone