Overexpression of CD133 promotes drug resistance in C6 glioma cells.

Overexpression of CD133 promotes drug resistance in C6 glioma cells.
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DOI:
10.1158/1541-7786.mcr-09-0383
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发表时间:
2010-08
期刊:
Molecular cancer research : MCR
影响因子:
--
通讯作者:
Lamé MW
Lamé MW
中科院分区:
其他
文献类型:
--
作者:
Angelastro JM;Lamé MW

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Glioblastoma multiforme is an extremely aggressive and clinically unresponsive form of cancer. Transformed neoplastic neural stem cells, resistant to chemo and radiation therapy, are thought to be responsible for the initial tumor formation and the recurrence of disease following surgical resection. These stem cells express multidrug resistance markers along with CD133. We show, that ectopic overexpression of CD133 in rat C6 glioma cells, leads to significant reluctance to undergo apoptosis from camptothecin and doxorubicin. Although p53 was upregulated in CD133 overexpressing glioma cells treated with DNA damaging agents, apoptosis appears to be p53-independent. At least one ABC transporter, rat P-glycoprotein/ ABCB1, was up regulated by 62% in CD133+ cells with a corresponding increase in activity. Thus, the combination of higher P-glycoprotein mRNA transcription and elevated transporter activity, appears to contribute to the protection from cytotoxic reagents. In conclusion, previous investigators have reported that resilient cancer stem cells co-express CD133 and ABC transporters with increased reluctance toward apoptosis. Our data suggest that CD133 may contribute to the observed resistance to apoptosis of CD133+ cancer stem cells.