Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer.
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.
Ohnishi
Shunsuke
S
Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Ohnami
Sumiko
S
Laub
Friedrich
F
Aoki
Kazunori
K
Suzuki
Koichi
K
Kanai
Yae
Y
Haga
Kazunori
K
Asaka
Masahiro
M
Ramirez
Francesco
F
Yoshida
Teruhiko
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D019656:Loss of Heterozygosity; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; C000715467:KLF4 protein, human; C492214:KLF5 protein, human; C000715468:Klf4 protein, mouse; C118391:Klf5 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors