Ohnishi Shunsuke, Ohnami Sumiko, Laub Friedrich, Aoki Kazunori, Suzuki Koichi, Kanai Yae, Haga Kazunori, Asaka Masahiro, Ramirez Francesco, Yoshida Teruhiko
Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Biochem Biophys Res Commun. 2003 Aug 22;308(2):251-6. doi: 10.1016/s0006-291x(03)01356-1.
Krüppel-like factors (KLFs) are key transcriptional regulators of cell differentiation and proliferation. Among the KLF family, the expression of KLF4 (GKLF) and KLF5 (IKLF) is highly restricted in the epithelial cells of several organs such as the gut and skin, and it has been reported that these epithelial-type KLF genes may be involved in colon carcinogenesis. Recently we found that Klf4 and Klf5 genes were significantly expressed in the developmental bladder epithelium of mice as well. Therefore, in this report we studied the involvement of the KLF4 and KLF5 genes in bladder carcinogenesis. First, we analyzed the expression of KLF4 and KLF5 in a variety of human bladder cancer cell lines and surgical specimens by RNA blot and in situ hybridization analyses. Both genes were highly expressed in the normal bladder epithelium, whereas KLF4, but not KLF5, was frequently downregulated in bladder cancer cell lines and cancer tissues. We then transduced the KLF4 and KLF5 genes into the bladder cancer cell lines using adenoviral vectors to examine the biological activities of the genes on those cells. The transduction of KLF4, but not KLF5, suppressed cell growth and induced apoptosis. Our study suggests that inactivation of KLF4 is one of the frequent steps towards bladder carcinogenesis.
Krüppel样因子（KLFs）是细胞分化和增殖的关键转录调节因子。在KLF家族中，KLF4（GKLF）和KLF5（IKLF）的表达在肠道和皮肤等多个器官的上皮细胞中受到高度限制，并且有报道称这些上皮型KLF基因可能参与结肠癌的发生。最近我们发现Klf4和Klf5基因在小鼠膀胱发育上皮中也有显著表达。因此，在本报告中，我们研究了KLF4和KLF5基因在膀胱癌发生中的作用。首先，我们通过RNA印迹和原位杂交分析，分析了KLF4和KLF5在多种人膀胱癌细胞系和手术标本中的表达。这两个基因在正常膀胱上皮中均高表达，而在膀胱癌细胞系和癌组织中，KLF4经常下调，而KLF5没有。然后，我们使用腺病毒载体将KLF4和KLF5基因导入膀胱癌细胞系，以检测这些基因对这些细胞的生物学活性。KLF4的转导抑制了细胞生长并诱导了凋亡，而KLF5没有。我们的研究表明，KLF4失活是膀胱癌发生过程中常见的步骤之一。
