癌变
胶质瘤
生物
下调和上调
癌症研究
细胞培养
癌症
神经干细胞
癌细胞
分子生物学
干细胞
细胞生物学
基因
遗传学
作者
Takuichiro Hide,Tatsuya Takezaki,Yuka Nakatani,Hideo Nakamura,Jun Ichi Kuratsu,Toru Kondo
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2009-10-14
卷期号:69 (20): 7953-7959
被引量:102
标识
DOI:10.1158/0008-5472.can-09-2006
摘要
Abstract Recent findings have shown that malignant tumors contain cancer-initiating cells (CIC), which self-renew and are tumorigenic. However, CICs have not been characterized properly due to lack of specific markers. We recently established a mouse glioma cell line, NSCL61, by overexpressing an oncogenic HRasL61 in p53-deficient neural stem cells. Using limiting dilution assays, we show that only 2 of 24 NSCL61 clones retained their tumorigenicity in vivo, although the others also expressed oncogenic HRasL61 and could proliferate in culture. A comparison of the gene expression profiles of tumorigenic and nontumorigenic clones showed that the tumorigenic clones had lost Sox11 expression. We show that overexpression of sox11 prevented tumorigenesis of NSCL61s by inducing their neuronal differentiation accompanied with decreased levels of plagl1. We also show that overexpression of plagl1 abolished neuronal commitment of nontumorigenic cells and induced them to become tumorigenic. Moreover, we show that human glioma-initiating cells lost sox11 expression, and overexpression of sox11 prevented their tumorigenesis in vivo. Together with the clinical evidence showing that downregulation of sox11 mRNA correlates with a significant decrease in survival, these findings suggest that Sox11 prevents gliomagenesis by blocking the expression of oncogenic plagl1. [Cancer Res 2009;69(20):7953–9]
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