The different role of Notch1 and Notch2 in astrocytic gliomas.
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.
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
Peng
P
Xu
Anling
A
Zhang
Rongcai
R
Jiang
Mingzhe
M
Qiu
Chunsheng
C
Kang
Zhifan
Z
Jia
Guangxiu
G
Wang
Lei
L
Han
Xing
X
Fan
Peiyu
P
Pu
D000818:Animals; D017209:Apoptosis; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt