中文摘要：

为研究p53缺失和K-ras突变在肺癌发生中的作用,建立了p53条件性敲除,K-ras^G12D条件性激活（p53^loxp/loxp、Lox-Stop-Lox-K-ras^G12D）的基因嵌合小鼠,获得条件性基因嵌合小鼠胚胎成纤维细胞（mouse embryonic fibroblasts,MEFs）。体外研究发现,内源性p53缺失协同K-ras^G12D的突变激活可促进MEFs的分裂、增殖和转化;体内研究证实,该协同突变激活可快速诱发肺部肿瘤的产生,组织病理学分析表明该肺癌类型为腺癌。上述研究工作为进一步认识p53和K-ras在肺癌发生发展中的作用打下了基础。

英文摘要：

To study the function of p53 loss and K-ras^G12D activation on lung tumorigenesis, we have constructed the hybrid mouse with a conditional knockout p53 allele and conditional knockin K-ras^G12D allele, obtained the hybrid mouse embryonic fibroblasts （MEFs）. In vitro studies have showed that activation of K-ras^G12D together with p53 loss in MEFs promoted the increased cell division, proliferation and transformation. In vivo studies have demonstrated that simultaneous activation of K-ras^G12D and p53 loss induced lung adenocarcinoma formation in mice.