Multifaceted analysis of molecular pathogenesis of human lung cancers

在这一研究项目中，多个事实的分析是根据人类肺癌的分子病理学进行的，以更好地理解。顺便说一下，我们成功地获得了以下的结果。（1）使用微阵列技术揭示了可确定的异质性存在的情况，并允许我们构建一个高准确度模型，以预测5年后的生存。在此期间，在蛋白质水平上也启动了表达式分析，将在此研究项目的下一个阶段进行适当的调查。（2）通过比较在我们实验室中建立的一个高度偏元和其父母人类肺癌细胞线的表达概况，与炎症和其他一些生物反应有关的各种分子表达方式，如血管生成和依赖蛋白质的退化被认为是在代谢过程中被纳入的。此外，我们也与孤立的新基因有关，包括CLCP 1和LNMO 1及其在Metastasis中的角色。（3）我们在肺癌患者中发现了持久性染色体不稳定性的存在，在p53中的一个间接作用，在获取染色体不稳定性表型中的激活作用。We also found a homozygous deletion of 14·3·3·at 17 p13. 3，a site of frequent alleic losses in lung cancers。这一发现使我们能够识别出14-3-3-3可以在肺癌中扮演G2检查点的角色。在补充剂中，我们在肺癌中找到了需要的不受影响的降低G2检查点，作为CHFR的频繁表皮沉默，基因在prophase检查点中被隐含。

In this research project, multi faceted analyses were conducted in order to better understand the molecular pathogenesis of human lung cancers. Consequently, we have successfully obtained the following results.(1) Expression profiling analysis of lung cancer specimens using the microarray technology revealed the presence of considerable heterogeneity and also allowed us to construct a highly accurate model for predicting 5-yr survival after potentially curative resection. Expression profiling at the protein level has also initiated during this period, which will be rigorously investigated in the next term of this research project.(2) By comparing expression profiles of a highly metastatic and its parental human lung cancer cell lines established in our laboratory, various molecules related to inflammation and some other biological responses such as angiogenesis and proteasome-dependent degradation were suggested to be involved in the process of metastasis. Further, we also isolated novel genes related to metastasis including CLCP1 and LNMO1 and characterized their roles in metastasis.(3) We found the presence of persistent chromosomal instability in lung cancers and an indirect role of p53 in activation in the acquisition of chromosomal instability phenotype. We also found a homozygous deletion of 14・3・3ε at 17p13.3,a site of frequent alleic losses in lung cancers. This finding led us to identify that 14-3-3ε may play a role in G2 check point response in lung cancers. In addition, we found requently impaired decatenation G2 checkpoint in lung cancers as well as frequent epigenetic silencing of CHFR, a gene implicated in the prophase checkpoint.