Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer

• Published in: Biochemical and biophysical research communications Vol. 308; no. 2; pp. 251 - 256
• Main Authors: Ohnishi, Shunsuke, Ohnami, Sumiko, Laub, Friedrich, Aoki, Kazunori, Suzuki, Koichi, Kanai, Yae, Haga, Kazunori, Asaka, Masahiro, Ramirez, Francesco, Yoshida, Teruhiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.08.2003
• Subjects: Adenoviridae - genetics; Animals; Apoptosis; Bladder cancer; Cell Division; DNA-Binding Proteins - genetics; Down-Regulation; Genes, Tumor Suppressor; Humans; KLF4; KLF5; Kruppel-Like Transcription Factors; Krüppel-like factor; Loss of Heterozygosity; Mice; Recombinant Proteins - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Trans-Activators - genetics; Transcription Factors - genetics; Transduction, Genetic; Tumor Cells, Cultured; Tumor suppressor; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; KLF5; KLF4; Bladder cancer; Tumor suppressor; Krüppel-like factor
• ISSN: 0006-291X; 1090-2104
• 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.