Role of Btg2 in the progression of a PDGF-induced oligodendroglioma model.

Role of Btg2 in the progression of a PDGF-induced oligodendroglioma model.
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DOI:
10.3390/ijms131114667
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发表时间:
2012-11-12
影响因子:
5.6
通讯作者:
Malatesta P
Malatesta P
中科院分区:
生物学2区
文献类型:
--
作者:
Appolloni I;Curreli S;Caviglia S;Barilari M;Gambini E;Pagano A;Malatesta P

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肿瘤进展是肿瘤学的一个关键方面。即使是强大的致癌刺激,如血小板衍生生长因子-B(PDGF-B)的过度表达本身也不足以赋予细胞完全的恶性。在以前的研究中,我们发现过度表达PDGF-B的神经前体细胞需要经历进展才能获得在移植后产生继发性肿瘤的能力。通过比较进展期前后PDGF表达细胞的表达谱,我们发现进展期肿瘤持续下调抗增殖基因Btg2的表达。因此,我们通过功能丧失和功能获得的实验测试了Btg2的下调对于神经胶质瘤的进展是否充分和必要。我们的结果表明,Btg2的下调是不够的,但对于肿瘤的进展是必要的,因为在完全进展的肿瘤中重新引入Btg2会显着削弱它们的胶质瘤生成潜力。这些结果表明Btg2在脑胶质瘤的发展过程中起着重要作用。根据这一观点,对人脑胶质瘤的公共数据集的分析表明,Btg2表达水平的降低与显著更差的预后相关。
Tumor progression is a key aspect in oncology. Not even the overexpression of a powerful oncogenic stimulus such as platelet derived growth factor-B (PDGF-B) is sufficient per se to confer full malignancy to cells. In previous studies we showed that neural progenitors overexpressing PDGF-B need to undergo progression to acquire the capability to give rise to secondary tumor following transplant. By comparing the expression profile of PDGF-expressing cells before and after progression, we found that progressed tumors consistently downregulate the expression of the antiproliferative gene Btg2. We therefore tested whether the downregulation of Btg2 is sufficient and necessary for glioma progression with loss and gain of function experiments. Our results show that downregulation of Btg2 is not sufficient but is necessary for tumor progression since the re-introduction of Btg2 in fully progressed tumors dramatically impairs their gliomagenic potential. These results suggest an important role of Btg2 in glioma progression. Accordingly with this view, the analysis of public datasets of human gliomas showed that reduced level of Btg2 expression correlates with a significantly worse prognosis.
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