Kruppel-like factor 4 (Gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G(1)/S progression of the cell cycle

Kruppel-like factor 4 (KLF4) is an epithelial cell-enriched, zinc finger-co ntaining transcription factor, the expression of which is associated with g rowth arrest. Previous studies show that constitutive expression of KLF4 in hibits DNA synthesis but the manner by which KLF4 exerts this effect is unc lear. In the present study, we developed a system in which expression of KL F4 is controlled by a promoter that is induced upon treatment of cells cont aining the receptors for the insect hormone, eedysone, with ponasterone A, an eedysone analogue. The rate of proliferation of a stably transfected col on cancer cell line, RKO, was significantly decreased following addition of ponasterone A when compared with untreated cells. Flow cytometric analyses indicated that the inducible expression of KLF4 caused a block in the G(1) /S phase of the cell cycle. A similar block was observed when eedysone rece ptor-containing RKO cells were infected with a replication-defective recomb inant adenovirus containing an inducible KLF4 and treated with ponasterone A. Results of these studies provide evidence that the inhibitory effect of KLF4 on cell proliferation is mainly exerted at the G(1)/S boundary of the cell cycle.