Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
PLoS One. 2013;8(1):e53654. doi: 10.1371/journal.pone.0053654. Epub 2013 Jan 21.
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.
众所周知，Notch 信号在各种肿瘤中根据细胞环境发挥致癌或抑癌作用。然而，在我们之前的研究中，我们发现 Notch1 在大多数不同分级的星形细胞瘤和神经胶质瘤细胞系 U251 和 A172 中过表达，而 Notch2 下调。我们通过 siRNA 在神经胶质瘤细胞中敲低 Notch1，发现细胞生长和侵袭受到抑制，而细胞凋亡在体外或体内均被诱导。为了进一步阐明 Notch2 在神经胶质瘤发病机制中的作用，本研究通过转染 Notch2 表达质粒在神经胶质瘤细胞中过表达 Notch2，并在体外和体内检测细胞生长、侵袭和凋亡，同时将靶向 Notch1 的 siRNA 用作体内阳性对照。结果表明，上调 Notch2 具有抑制细胞生长和侵袭以及诱导细胞凋亡的作用，与敲低 Notch1 的结果相同。同时，星形细胞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 Notch1 和 Notch2 在星形细胞瘤的生物学过程中发挥不同的作用。敲低 Notch1 或过表达 Notch2 均可调节星形细胞瘤表型， Notch1 和 Notch2 在胶质瘤生长中发挥不同作用的机制尚需进一步研究。
