LRIG1 dictates the chemo-sensitivity of temozolomide (TMZ) in U251 glioblastoma cells via down-regulation of EGFR/topoisomerase-2/Bcl-2

被引：36

作者：

Qi, Xu-chen ^{[1
]}

Xie, Da-jiang ^{[1
]}

Yan, Qing-feng ^{[2
]}

Wang, Yi-rong ^{[1
]}

Zhu, Yin-xin ^{[1
]}

Qian, Cong ^{[1
]}

Yang, Shu-xu ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Med Sci, Dept Neurosurg, Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Life Sci, Hangzhou 310058, Zhejiang, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 437卷 / 04期

关键词：

LRIG1; Temozolomide; EGFR; Topoisomerase-2; Bcl-2; Glioblastoma; GROWTH-FACTOR RECEPTOR; GLIOMA-CELLS; CANCER CELLS; METHYLTRANSFERASE MGMT; RNA INTERFERENCE; ACTIVATION; INHIBITOR; APOPTOSIS; EXPRESSION; MULTIFORME;

D O I：

10.1016/j.bbrc.2013.06.116

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the current study, we aimed to understand the potential role of leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) in TMZ-resistance of U251 glioma cells. We established TMZ-resistant U251 clones (U251/TMZ cells), which expressed low level of LRIG1, but high levels of epidermal growth factor receptor (EGFR), topoisomerase-2 (Topo-2) and Bcl-2. Depletion of LRIG1 by the targeted RNA interference (RNAi) upregulated EGFR/Topo-2/Bcl-2 in U251 cells, and the cells were resistant to TMZ. Reversely, over-expression of LRIG1 in U251 cells downregulated EGFR/Topo-2/Bcl-2 expressions, and cells were hyper-sensitive to TMZ. Our data suggested EGFR-dependent mammalian target of rapamycin (mTOR) activation was important for Topo-2 and Bcl-2 expressions in U251/TMZ cells. The EGFR inhibitor and the mTOR inhibitor downregulated Topo-2/Bcl-2 expressions, both inhibitors also restored TMZ sensitivity in U251/TMZ cells. Finally, inhibition of Topo-2 or Bcl-2 by targeted RNAi(s) knockdown or by the corresponding inhibitor re-sensitized U251/TMZ cells to TMZ, indicating that both Topo-2 and Bcl-2 were important for TMZ resistance in the resistant U251 cells. Based on these results, we concluded that LRIG1 inhibits EGFR expression and the downstream signaling activation, interferes with Bcl-2/Topo-2 expressions and eventually sensitizes glioma cells to TMZ. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：565 / 572

页数：8

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