Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines
Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines
复制标题
DOI：
10.1007/s00280-009-1151-1
复制
发表时间：
2010-07
影响因子：
3
通讯作者：
Y. Horio;H. Osada;J. Shimizu;S. Ogawa;T. Hida;Y. Sekido
中科院分区：
文献类型：
--
作者：
Y. Horio;H. Osada;J. Shimizu;S. Ogawa;T. Hida;Y. Sekido
目的RanBP 2是一种小的泛素样DNA拓扑异构酶II（TopoII）修饰连接酶，在有丝分裂过程中通过将TopoII募集到着丝粒上来维持染色体稳定。据报道，具有低量RanBP 2的工程小鼠形成肺腺癌。此外，在鼠胚胎成纤维细胞中，已报道了后期染色质桥的形成，这是TopoII化学抑制导致DNA脱连环受损的细胞的一个显著特征。在这项研究中，我们测试是否RanBP 2基因的mRNA表达和化疗敏感性的TopoII抑制剂，amrubicin.MethodsUsing一个面板的20个肺癌细胞株之间的关联，RanBP 2，TopoII-α和TopoII-β基因的mRNA表达水平进行了研究，通过定量实时逆转录PCR。氨柔比星的体外细胞毒性进行了评估，使用基于四氮唑的比色法（MTT法）。ResultsAlthough RanBP 2 mRNA的表达很少下调，在人肺癌细胞系，显着较高的RanBP 2的成绩单，观察小细胞肺癌比非小细胞肺癌。氨柔比星的化疗敏感性和mRNA表达水平的RanBP 2，TopoII-α和TopoII-β genes.ConclusionsOur的体外结果表明，RanBP 2和TopoII亚型的mRNA表达不太可能是一个预测的生物标志物的敏感性氨柔比星之间没有相关性。
PurposeRanBP2 is a small ubiquitin-like modifier ligase for DNA topoisomerase II (TopoII) and plays a role in maintaining chromosome stability by recruiting TopoII to centromeres during mitosis. Engineered-mice with low amounts of RanBP2 have been reported to form lung adenocarcinomas. Furthermore, in the murine embryonic fibroblasts, formation of chromatin bridges in anaphase, a distinctive feature of cells with impaired DNA decatenation by chemical inhibition of TopoII, has been reported. In this study, we tested whether the association between mRNA expression of the RanBP2 gene and chemosensitivity of a TopoII inhibitor, amrubicin could be seen.MethodsUsing a panel of 20 lung cancer cell lines, the mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes were examined by quantitative real-time reverse transcription PCR. The in vitro cytotoxicity of amrubicin was assessed using a tetrazolium-based colorimetric assay (MTT assay).ResultsAlthough RanBP2 mRNA expression was infrequently downregulated in human lung cancer cell lines, significantly higher RanBP2 transcripts were observed in small cell lung cancer than non-small cell lung cancer. There were no correlations between chemosensitivity of amrubicin and mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes.ConclusionsOur in vitro results suggest that mRNA expressions of RanBP2 and TopoII isoforms are unlikely to be a predictive biomarker for the sensitivity to amrubicin.