Genes and molecular pathways related to radioresistance of oral squamous cell carcinoma cells
Genes and molecular pathways related to radioresistance of oral squamous cell carcinoma cells
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DOI：
10.1002/ijc.22561
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发表时间：
2007-05-15
影响因子：
6.4
通讯作者：
Tanzawa, Hideki
中科院分区：
文献类型：
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作者：
Ishigami, Takashi;Uzawa, Katsuhiro;Tanzawa, Hideki
为了鉴定与放射抵抗性口腔鳞状细胞癌（OSCC）相关的基因，我们比较了OSCC细胞系表现出放射抵抗性和放射敏感性细胞之间的基因表达特征，X射线照射后，以剂量依赖的方式，使用Affytek基因芯片分析与人类基因组-U133加2.0基因芯片。微阵列数据确定了167个基因，这些基因在X射线照射后在抗辐射细胞中显著过表达。在所鉴定的基因中，40个被映射到由不相容性途径分析工具鉴定的3个高度显著的遗传网络。基因本体分析表明，与癌症相关的功能具有最高的意义。这40个基因包括25个形成I网络的癌症相关基因，并按功能分类为生长和增殖、凋亡和粘附。实时定量逆转录聚合酶链反应结果显示，辐射抗性细胞中25个基因的mRNA表达水平均高于辐射敏感细胞，且呈剂量依赖性和时间依赖性。我们的研究结果表明，确定的基因有助于阐明放射抵抗的分子机制，口腔鳞癌的放射性分子标记，选择合适的放射治疗这种疾病。(c)2007 Wiley-Liss，Inc.
To identify genes associated with radioresistant oral squamous cell carcinoma (OSCC), we compared gene expression signatures between OSCC cell lines exhibiting radioresistance and cells with radiosensitivity after X-ray irradiation in a dose-dependent manner using Affymetrix GeneChip analysis with Human Genome-U133 plus 2.0 GeneChip. The microarray data identified 167 genes that were significantly overexpressed in radioresistant cells after X-ray irradiation. Among the genes identified, 40 were mapped to 3 highly significant genetic networks identified by the Ingenuity Pathway Analysis tool. Gene ontology analysis showed that cancer-related function had the highest significance. The 40 genes included 25 cancer-related genes that formed I network and were categorized by function into growth and proliferation, apoptosis, and adhesion. Furthermore, real-time quantitative reverse transcriptase-polymerase chain reaction showed that the mRNA expression levels of the 25 genes were higher in radioresistant cells than in radiosensitive cells in a dose-dependent manner and in a time-dependent manner. Our results suggest that the identified genes help to elucidate the molecular mechanisms of the radioresistance of OSCC and could be radiotherapeutic molecular markers for choosing the appropriate radiotherapy for this disease. (c) 2007 Wiley-Liss, Inc.