Identification of differentially expressed genes contributing to radioresistance in lung cancer cells using microarray analysis
Identification of differentially expressed genes contributing to radioresistance in lung cancer cells using microarray analysis
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DOI：
10.1667/rr3401
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Wang, SQ
中科院分区：
文献类型：
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作者：
Guo, WF;Lin, RX;Wang, SQ
在许多癌症患者中，放疗在控制肿瘤生长方面发挥了关键作用。在一个疗程的放疗后，通常很难确定肿瘤细胞群中有多少部分具有放射耐药性。肿瘤细胞对辐射的反应被认为伴随着基因表达模式的复杂变化。有可能使用这些药物使放射耐药肿瘤细胞增敏并提高放射治愈率。基于电离辐射的生物学效应，本研究开发了一种寡核苷酸芯片，分析了143个基因在两种不同放射敏感性的肺癌细胞系细胞中的表达。与NCI-H446细胞相比，A549细胞中18个基因的表达水平显著升高，其中8个基因表达上调，10个基因表达下调。在5gy辐照A549细胞中，辐照后6 h和24 h分别有22个（上调19个，下调3个）和26个（上调8个，下调18个）差异表达基因。在NCI-H446细胞中，辐照后6 h和24 h，分别有17个（9个上调，8个下调）和18个（6个上调，12个下调）基因的表达发生改变。RT-PCR检测发现，辐照后A549细胞中MDM2、BCL2、PKCZ和PIM2表达水平升高，NCI-11446细胞中表达水平降低。与NCI-H446细胞相比，A549细胞中参与DNA修复的基因如XRCC5、ERCC5、ERCC1、RAD9A、ERCC4和编码DNA- pk的基因水平升高。MDM2的反义抑制导致A549细胞的放射敏感性增加。综上所述，这些结果表明，一组参与DNA修复、细胞周期调节、细胞增殖和凋亡的基因可能是导致这两种肺癌细胞辐射抗性不同的原因。这一基因列表可能有助于使放射耐药肺癌细胞增敏。(c) 2005年辐射研究学会。
Radiotherapy has played a key role in the control of tumor growth in many cancer patients. It is usually difficult to determine what fraction of the tumor cell population is radioresistant after a course of radiotherapy. The response of tumor cells to radiation is believed to be accompanied by complex changes in the gene expression pattern. It may be possible to use these to sensitize radioresistant tumor cells and improve radiocurability. Based on the biological effects of ionizing radiation, in the present study, we developed one oligonucleotide microarray to analyze the expression of 143 genes in cells of two lung cancer cell lines with different radiosensitivities. Compared to NCI-H446 cells, expression of 18 genes significantly increased the basal levels in the radioresistant A549 cells, in which eight genes were up-regulated and 10 genes were down-regulated. In A549 cells irradiated with 5 Gy, 22 (19 up-regulated and three down-regulated) and 26 (eight upregulated and 18 down-regulated) differentially expressed genes were found 6 and 24 h after irradiation, respectively. In NCI-H446 cells, the expression of 17 (nine up-regulated and eight down-regulated) and 18 (six up-regulated and 12 downregulated) genes was altered 6 and 24 h after irradiation, respectively. RT-PCR was performed, and we found that MDM2, BCL2, PKCZ and PIM2 expression levels were increased in A549 cells and decreased in NCI-11446 cells after irradiation. Genes involved in DNA repair, such as XRCC5, ERCC5, ERCC1, RAD9A, ERCC4 and the gene encoding DNA-PK, were found to be increased to a higher level in A549 cells than in NCI-H446 cells. Antisense suppression of MDM2 resulted in increased radiosensitivity of A549 cells. Taken together, these results demonstrate the possibility that a group of genes involved in DNA repair, regulation of the cell cycle, cell proliferation and apoptosis is responsible for the different radioresistance of these two lung cancer cells. This list of genes may be useful in attempts to sensitize the radioresistant lung cancer cells. (c) 2005 by Radiation Research Society.