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

Shunsuke Ohnishi, Sumiko Ohnami, Friedrich Laub, Kazunori Aoki, Koichi Suzuki, Yae Kanai, Kazunori Haga, Masahiro Asaka, Francesco Ramirez, Teruhiko Yoshida

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147 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume308
Issue number2
DOIs
Publication statusPublished - 2003 Aug 22
Externally publishedYes

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Keywords

  • Bladder cancer
  • KLF4
  • KLF5
  • Krüppel-like factor
  • Tumor suppressor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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