The different role of Notch1 and Notch2 in astrocytic gliomas.
The different role of Notch1 and Notch2 in astrocytic gliomas.
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DOI：
10.1371/journal.pone.0053654
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Pu P
中科院分区：
文献类型：
--
作者：
Xu P;Zhang A;Jiang R;Qiu M;Kang C;Jia Z;Wang G;Han L;Fan X;Pu P
众所周知，Notch 信号传导在多种肿瘤中发挥致癌或肿瘤抑制作用，具体取决于细胞环境。然而，在我们之前的研究中，我们发现Notch1在大多数不同级别的星形细胞胶质瘤以及胶质母细胞瘤细胞系U251和A172中过度表达，而Notch2下调。我们通过siRNA敲低胶质母细胞瘤细胞中的Notch1，并发现细胞生长和侵袭受到抑制，而细胞凋亡在体外或体内被诱导。为了进一步阐明Notch2在胶质瘤发病机制中的作用，本研究通过转染Notch2表达质粒在胶质瘤细胞中强制过表达Notch2，并在体外和体内检测细胞的生长、侵袭和凋亡，并使用靶向Notch1的siRNA作为体内阳性对照。结果显示，上调Notch2具有抑制细胞生长和侵袭、诱导细胞凋亡的作用，与敲低Notch1的结果相同。同时，星形胶质瘤细胞中核心信号通路EGFR/PI3K/AKT的活性受到抑制。因此，本研究首次揭示了Notch1和Notch2在星形细胞胶质瘤的生物学过程中发挥着不同的作用。敲低Notch1或强制过度表达Notch2均可调节星形细胞胶质瘤表型，Notch1和2在胶质瘤生长中发挥不同作用的机制应进一步研究。
It is well known that Notch signaling plays either oncogenic or tumor suppressive role in a variety of tumors, depending on the cellular context. However, in our previous study, we found that Notch1 was overexpressed while Notch2 downregulated in the majority of astrocytic gliomas with different grades as well as in glioblastoma cell lines U251 and A172. We had knocked down Notch1 by siRNA in glioblastoma cells, and identified that the cell growth and invasion were inhibited, whereas cell apoptosis was induced either in vitro or in vivo. For further clarification of the role of Notch2 in pathogenesis of gliomas, enforced overexpression of Notch2 was carried out with transfection of Notch2 expression plasmid in glioma cells and the cell growth, invasion and apoptosis were examined in vitro and in vivo in the present study, and siRNA targeting Notch1 was used as a positive control in vivo. The results showed that upregulating Notch2 had the effect of suppressing cell growth and invasion as well as inducing apoptosis, just the same as the results of knocking down Notch1. Meanwhile, the activity of core signaling pathway–EGFR/PI3K/AKT in astrocytic glioma cells was repressed. Thus, the present study reveals, for the first time, that Notch1 and Notch2 play different roles in the biological processes of astrocytic gliomas. Knocking down the Notch1 or enforced overexpression of Notch2 both modulate the astrocytic glioma phenotype, and the mechanism by which Notch1 and 2 play different roles in the glioma growth should be further investigated.
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影响因子：
3.7
作者：
Brennan C;Momota H;Hambardzumyan D;Ozawa T;Tandon A;Pedraza A;Holland E
通讯作者：
Holland E
影响因子：
--
作者：
McKenzie G;Ward G;Stallwood Y;Briend E;Papadia S;Lennard A;Turner M;Champion B;Hardingham GE
通讯作者：
Hardingham GE
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K
影响因子：
8
作者：
Fitzgerald, K;Harrington, A;Leder, P
通讯作者：
Leder, P
影响因子：
11.2
作者：
Purow, BW;Haque, RM;Fine, HA
通讯作者：
Fine, HA