Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4, but not KLF5, in bladder cancer
Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4, but not KLF5, in bladder cancer
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DOI：
10.1016/s0006-291x(03)01356-1
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发表时间：
2003-08-22
影响因子：
3.1
通讯作者：
Yoshida, T
中科院分区：
文献类型：
--
作者：
Ohnishi, S;Ohnami, S;Yoshida, T
Kruppel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)在肠道和皮肤等器官的上皮细胞中表达高度受限，已有报道这些上皮型KLF基因可能参与结肠癌的发生。最近我们发现KLF4和KLF5基因在小鼠的发育期膀胱上皮细胞中也有显著表达。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细胞中高表达，而KLF4，而不是KLF5，在膀胱癌细胞系和癌组织中经常下调。然后，我们用腺病毒载体将KLF4和KLF5基因导入膀胱癌细胞系，以检测这些基因在这些细胞上的生物学活性。KLF4的转导抑制了细胞的生长，而不是KLF5的转导，诱导了细胞的凋亡。我们的研究表明，KLF4失活是导致膀胱癌发生的常见步骤之一。(C)2003 Elsevier Inc.保留所有权利。
Kruppel-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. (C) 2003 Elsevier Inc. All rights reserved.