Inoue Ryo, Matsuyama Hideyasu, Yano Seiji, Yamamoto Yoshiaki, Iizuka Norio, Naito Katsusuke
Department of Urology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Anticancer Res. 2006 Nov-Dec;26(6B):4195-202.
The aim of this study was to identify key genes linked to the molecular action of gefitinib, a promising anticancer agent on human bladder cancer cell lines.
cDNA microarrays were used to profile feature genes in 5637 and T24 cells before and after treatment with gefitinib. PCR-based direct sequencing and Western blot analysis were performed to examine the mutation status and protein levels of EGFR in the cell lines.
Gefitinib significantly inhibited the proliferation of 5637 cells, while showing little inhibitory effect on T24 cells. Theses effects were independent of the mutation status and protein levels of EGFR. cDNA microarray analysis identified 15 feature genes classified as a cell cycle, apoptotic pathway and transcription. Notably, levels of expression of the cell invasion-related genes, YY1 and E-cadherin, were increased in 5637 cells sensitive to gefitinib.
Unique genes involved in the action of gefitinib were identified. Particularly, the upregulation of YY1 and E-cadherin may account for the efficacy of gefitinib in bladder cancer.
本研究旨在鉴定与吉非替尼（一种对人膀胱癌细胞系有前景的抗癌药物）分子作用相关的关键基因。
利用cDNA微阵列分析吉非替尼处理前后5637和T24细胞中的特征基因。采用基于PCR的直接测序和蛋白质印迹分析检测细胞系中表皮生长因子受体（EGFR）的突变状态和蛋白水平。
吉非替尼显著抑制5637细胞的增殖，而对T24细胞几乎没有抑制作用。这些作用与EGFR的突变状态和蛋白水平无关。cDNA微阵列分析鉴定出15个特征基因，分为细胞周期、凋亡途径和转录相关基因。值得注意的是，在对吉非替尼敏感的5637细胞中，细胞侵袭相关基因YY1和E-钙黏蛋白的表达水平升高。
鉴定出了参与吉非替尼作用的独特基因。特别是，YY1和E-钙黏蛋白的上调可能解释了吉非替尼在膀胱癌中的疗效。
