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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Nrf2 is required to maintain the self-renewal of glioma stem cells

Authors: Jianhong Zhu, Handong Wang, Qing Sun, Xiangjun Ji, Lin Zhu, Zixiang Cong, Yuan Zhou, Huandong Liu, Mengliang Zhou

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioma stem cells (GSCs). Self-renewal is a complex biological process necessary for maintaining the glioma stem cells. Nuclear factor rythroid 2-related factor 2(Nrf2) plays a significant role in protecting cells from endogenous and exogenous stresses. Nrf2 is a key nuclear transcription factor that regulates antioxidant response element (ARE)-containing genes. Previous studies have demonstrated the significant role of Nrf2 in the proliferation of glioblastoma, and in their resistance to radioactive therapies. We examined the effect of knocking down Nrf2 in GSCs.

Methods

Nrf2 expression was down-regulated by shRNA transinfected with lentivirus. Expression levels of Nestin, Nrf2, BMI-1, Sox2 and Cyclin E were assessed by western blotting, quantitative polymerase chain reaction (qPCR) and immunohistochemistry analysis. The capacity for self-renewal in vitro was assessed by genesis of colonies. The capacity for self-renewal in vivo was analyzed by tumor genesis of xenografts in nude mice.

Results

Knockdown of Nrf2 inhibited the proliferation of GSCs, and significantly reduced the expression of BMI-1, Sox2 and CyclinE. Knocking down of Nrf2 changed the cell cycle distribution of GSCs by causing an uncharacteristic increase in the proportion of cells in the G2 phase and a decrease in the proportion of cells in the S phase of the cell cycle.

Conclusions

Nrf2 is required to maintain the self-renewal of GSCs, and its down-regulation can attenuate the self-renewal of GSCs significantly.
Appendix
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Metadata
Title
Nrf2 is required to maintain the self-renewal of glioma stem cells
Authors
Jianhong Zhu
Handong Wang
Qing Sun
Xiangjun Ji
Lin Zhu
Zixiang Cong
Yuan Zhou
Huandong Liu
Mengliang Zhou
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-380

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