Axin gene methylation status correlates with radiosensitivity of lung cancer cells.
Axin gene methylation status correlates with radiosensitivity of lung cancer cells.
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Axin基因甲基化状态与肺癌细胞的放射敏感性相关
DOI：
10.1186/1471-2407-13-368
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发表时间：
2013-08-02
期刊：
影响因子：
3.8
通讯作者：
Wang EH
中科院分区：
文献类型：
--
作者：
Yang LH;Han Y;Li G;Xu HT;Jiang GY;Miao Y;Zhang XP;Zhao HY;Xu ZF;Stoecker M;Wang E;Xu K;Wang EH
背景我们之前报道Axin1（Axin）在许多肺癌病例中下调，X射线照射增加Axin表达并抑制肺癌细胞。但其机制尚不清楚。方法采用4种肺癌细胞系，在X射线照射或未照射的情况下检测Axin的甲基化状态。使用实时PCR来定量Axin的表达，并应用蛋白质印迹分析来测量Axin、β-catenin、Cyclin D1、MMP-7、DNMTS、MeCP2和乙酰化组蛋白的蛋白水平。采用流式细胞术分析、集落形成实验、Transwell实验和异种移植物生长实验研究X射线处理后Axin基因高甲基化或非甲基化的细胞的生物学行为。结果4个细胞系中有2个检测到高甲基化Axin基因，且与Axin表达呈负相关。 X射线处理显着上调H446和H157细胞中的Axin表达，这些细胞具有Axin基因的内在高甲基化(P<0.01)，但在具有非甲基化Axin基因的LTE和H460细胞中没有表现出上调。 2Gy X 射线显着减少了 H157 细胞中的集落形成（从 71% 减少到 10.5%），而 LTE 细胞中的减少程度较低（从 71% 减少到 20%）。 X射线照射后，与LTE细胞（从1.06 g到0.65 g）相比，H157细胞（从1.15 g到0.28 g）的异种移植物生长显着下降。 X射线照射后的H157细胞的细胞侵袭力显着降低，细胞凋亡增加（P<0.01）。在肺癌细胞中可以检测到DNMTs和MeCP2的下调以及乙酰化组蛋白的上调。结论X射线诱导的肺癌细胞抑制可能是通过基因组DNA去甲基化和组蛋白乙酰化增强Axin表达来介导的。不同Axin基因甲基化状态的肺癌细胞表现出不同的放射敏感性，提示Axin基因甲基化状态可能是预测肿瘤放射敏感性的重要因素之一。
BackgroundWe previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear.MethodsFour lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment.ResultsHypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells.ConclusionsX-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor to predict radiosensitivity of the tumor.
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DOI：
10.1016/j.bbrc.2004.06.081
发表时间：
2004-08-06
影响因子：
3.1
作者：
Pogribny, I;Raiche, J;Kovalchuk, O
通讯作者：
Kovalchuk, O
影响因子：
8
作者：
Koturbash, I.;Rugo, R. E.;Kovalchuk, O.
通讯作者：
Kovalchuk, O.
DOI：
10.1016/j.mrfmmm.2003.12.016
发表时间：
2004-04-14
影响因子：
2.3
作者：
Kovalchuk, O;Burke, P;Pogribny, I
通讯作者：
Pogribny, I
影响因子：
4.2
作者：
Miao, JY;Kusafuka, T;Okada, A
通讯作者：
Okada, A
DOI：
10.1016/j.bbrc.2004.10.002
发表时间：
2004-12-03
影响因子：
3.1
作者：
Raiche, J;Rodriguez-Juarez, R;Kovalchuk, O
通讯作者：
Kovalchuk, O