Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, China.
J Cancer Res Clin Oncol. 2011 Dec;137(12):1739-47. doi: 10.1007/s00432-011-1050-9. Epub 2011 Sep 10.
To find new signaling pathways that may be involved in the cellular response to ionizing radiation.
Two radioresistant subclones (A549/R and SPCA1/R) derived from lung adenocarcinoma cell lines A549 and SPCA1 were established after eight rounds of sublethal irradiation. The new subclones were tested for radioresistant features using clonogenic assay and apoptosis analysis. The genes expressed differentially were screened with cDNA microarray analysis consisting of 48,000 transcript probes and confirmed by quantitative real-time PCR.
Stable and significant radioresistance was observed in the screened subclones. The microarray analysis showed 65 genes were up-regulated and 141 genes down-regulated in SPCA1/R cells. The up-regulated and down-regulated genes were 708 and 230 in A549/R cells, respectively. Twenty-seven altered genes were consistent in both subclones. Interestingly, members the of human solute carrier (SLC) gene superfamily were among in 27 genes.
The differentially expressed genes in both cell lines may contribute to their radioresistant phenotype. This extensive list of genes identified in the experiment provides a large body of potentially valuable information for studying the molecular mechanism(s) of radiosensitivity and identification of candidate molecular markers of radiation sensitivity. Thus, to our knowledge, the SLC gene superfamily is the first being reported to involve in acquired radioresistance.
寻找可能参与细胞对电离辐射反应的新信号通路。
从肺腺癌细胞系 A549 和 SPCA1 中建立了 8 轮亚致死照射后衍生的 2 个耐辐射亚克隆（A549/R 和 SPCA1/R）。使用集落形成试验和细胞凋亡分析测试新亚克隆的耐辐射特征。使用包含 48000 个转录探针的 cDNA 微阵列分析筛选差异表达的基因，并通过定量实时 PCR 进行确认。
筛选出的亚克隆表现出稳定且显著的耐辐射性。微阵列分析显示 SPCA1/R 细胞中 65 个基因上调，141 个基因下调。A549/R 细胞中上调和下调的基因分别为 708 和 230。在两个亚克隆中都有 27 个改变的基因是一致的。有趣的是，人类溶质载体（SLC）基因超家族的成员也在这 27 个基因中。
这两个细胞系中差异表达的基因可能有助于其耐辐射表型。该实验中鉴定的大量基因提供了大量有价值的信息，可用于研究放射敏感性的分子机制和鉴定候选的辐射敏感性分子标记。因此，据我们所知，SLC 基因超家族是第一个被报道参与获得性耐辐射的基因超家族。
