Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland.
J Physiol Pharmacol. 2017 Apr;68(2):209-214.
Phosphate-activated glutaminase (GA), a ubiquitous glutamine-metabolizing enzyme, is encoded by two genes, GLS and GLS2. In mammalian cancers, GLS isoforms are perceived as molecules promoting cell proliferation and invasion, whereas the role of GLS2 isoforms seems to be more complex and cell type-specific. Previous studies have shown abundance of GLS and lack of GLS2 transcripts in T98G human glioblastoma (GBM) cell line and patient-derived GBM. Transfection with GAB sequence, the whole GLS2 cDNA transcript, suppressed malignant phenotype of T98G cells. Microarray analysis revealed upregulation of GATA3, the product of which has been implicated in suppressing growth of some peripheral cancers. In this study we confirmed a significant upregulation of GATA3 expression in the transfected cells both at mRNA and protein level. Considerable expression of GATA3 was also observed in GBM tissues (previously shown as not expressing GLS2), while only traces or no GATA3 was detected in (GLS2-expressing) non-tumorigenic brain samples. In conclusion, while mechanistic relation between GAB and GATA3 expression is evident following in vitro manipulation of GBM cell line, it does not appear to be an intrinsic property of GBM nor non-tumorigenic brain tissue.
磷酸化谷氨酰胺酶（GA）是一种普遍存在的谷氨酰胺代谢酶，由两个基因 GLSl 和 GLS2 编码。在哺乳动物癌症中，GLSl 同工酶被认为是促进细胞增殖和侵袭的分子，而 GLS2 同工酶的作用似乎更为复杂，且具有细胞类型特异性。先前的研究表明，在 T98G 人胶质母细胞瘤（GBM）细胞系和患者来源的 GBM 中，GLS 丰度高，而 GLS2 转录本缺失。用 GAB 序列（GLS2 全长 cDNA 转录本）转染可抑制 T98G 细胞的恶性表型。微阵列分析显示 GATA3 的表达上调，其产物已被证实可抑制某些外周癌症的生长。在本研究中，我们在 mRNA 和蛋白水平上均证实了转染细胞中 GATA3 表达的显著上调。在 GBM 组织中也观察到了相当数量的 GATA3 表达（先前显示不表达 GLS2），而在（表达 GLS2）非致瘤性脑组织样本中仅检测到少量或无 GATA3。总之，虽然在体外操纵 GBM 细胞系后，GAB 和 GATA3 表达之间的机制关系是明显的，但它似乎不是 GBM 或非致瘤性脑组织的内在特性。
