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中枢神经系统组织和中枢神经系统肿瘤中编码谷氨酰胺酶同工型的mRNA的相对表达。

Relative expression of mRNAS coding for glutaminase isoforms in CNS tissues and CNS tumors.

作者信息

Szeliga Monika, Matyja Ewa, Obara Marta, Grajkowska Wiesława, Czernicki Tomasz, Albrecht Jan

机构信息

Department of Neurotoxicology, M. Mossakowski Medical Research Center, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland.

出版信息

Neurochem Res. 2008 May;33(5):808-13. doi: 10.1007/s11064-007-9507-6. Epub 2007 Oct 17.

Abstract

Glutaminase (GA) in mammalian tissues occurs in three isoforms: LGA (liver-type), KGA (kidney-type) and GAC (a KGA variant). Our previous study showed that human malignant gliomas (WHO grades III and IV) lack expression of LGA mRNA but are enriched in GAC mRNA relative to KGA mRNA. Here we analyzed the expression of mRNAs coding for the three isoforms in the biopsy material derived from other central nervous system tumors of WHO grades I-III. Non-neoplastic resective epileptic surgery samples served as control, as did cultured rat astrocytes and neurons. The GAC mRNA/KGA mRNA expression ratio was as a rule higher in the neoplastic than in control tissues, irrespective of the cell type dominating in the tumor or tumor malignancy. LGA mRNA expression was relatively very low in cultured astrocytes, and very low to absent in astrocytoma pilocyticum, ependymoma and subependymal giant cell astrocytoma (SEGA), tumors of astrocytic origin. LGA mRNA expression was almost as high as that of KGA and GAC mRNA in cultured neurons and epileptic surgery samples which were enriched in neurons. LGA mRNA was also relatively high in ganglioglioma which contains a discernable proportion of neuronal cells, and in oligodendroglioma. The results show that low expression of LGA mRNA is a feature common to normal astrocytes and astroglia-derived tumor cells or ependymomas and can be considered as a cell-type, rather than a malignancy marker.

摘要

谷氨酰胺酶(GA)在哺乳动物组织中以三种同工型存在:LGA(肝型)、KGA(肾型)和GAC(KGA变体)。我们之前的研究表明,人类恶性胶质瘤(世界卫生组织III级和IV级)缺乏LGA mRNA表达,但相对于KGA mRNA,GAC mRNA含量丰富。在此,我们分析了世界卫生组织I - III级其他中枢神经系统肿瘤活检材料中编码这三种同工型的mRNA的表达情况。非肿瘤性切除性癫痫手术样本作为对照,培养的大鼠星形胶质细胞和神经元也作为对照。无论肿瘤中占主导地位的细胞类型或肿瘤恶性程度如何,肿瘤组织中GAC mRNA/KGA mRNA表达比值通常高于对照组织。在培养的星形胶质细胞中,LGA mRNA表达相对非常低,在毛细胞型星形细胞瘤、室管膜瘤和室管膜下巨细胞星形细胞瘤(SEGA)等星形细胞起源的肿瘤中,LGA mRNA表达非常低甚至缺失。在富含神经元的培养神经元和癫痫手术样本中,LGA mRNA表达几乎与KGA和GAC mRNA一样高。在含有一定比例可识别神经元细胞的神经节胶质瘤和少突胶质细胞瘤中,LGA mRNA也相对较高。结果表明,LGA mRNA低表达是正常星形胶质细胞和星形胶质细胞来源的肿瘤细胞或室管膜瘤共有的特征,可被视为一种细胞类型标志物,而非恶性标志物。

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