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Expression of PPARγ and Its Ligand‐dependent Growth Inhibition in Human Brain Tumor Cell Lines

机译:PPARγ在人脑肿瘤细胞系中的表达及其配体依赖性生长抑制

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摘要

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.
机译:过氧化物酶体增殖物激活受体y(PPARγ)属于甲状腺/类固醇激素受体的超家族,并以配体依赖性方式调节其靶基因的转录。最近,据报道PPARγ在源自乳腺癌,结肠癌,胃癌和肺癌的几种细胞系中表达。 PPARγ的配体激活抑制了这些肿瘤细胞的生长,表明PPARγ配体是表达PPARγ的肿瘤中潜在的抗癌药。然而,尚未研究其在脑肿瘤中的表达。因此,我们研究了来自20名患者的不同病理分期的神经胶质瘤样品中的表达。已证明95%的神经胶质瘤组织表达PPARγmRNA。该结果促使我们研究PPARγ配体是否影响源自脑肿瘤的细胞系的生长。在源自恶性神经胶质瘤或神经母细胞瘤的9种细胞系中研究了受体表达。在神经胶质瘤细胞系SK‐MG-1和神经母细胞瘤细胞系NB-1中检测到表达。 PPARγ配体之一曲格列酮的添加诱导了两种细胞系的生长抑制。进一步的分析表明,这种生长抑制是由PPARγ介导的凋亡诱导引起的。这些结果表明,PPARγ配体可能是治疗表达该受体的脑肿瘤的潜在治疗剂。

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