Krüppel-like factor 4 (gut-enriched Krüppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle.
Krüppel-like factor 4 (KLF4) is an epithelial cell-enriched, zinc finger-containing transcription factor, the expression of which is associated with growth arrest. Previous studies show that constitutive expression of KLF4 inhibits DNA synthesis but the manner by which KLF4 exerts this effect is unclear. In the present study, we developed a system in which expression of KLF4 is controlled by a promoter that is induced upon treatment of cells containing the receptors for the insect hormone, ecdysone, with ponasterone A, an ecdysone analogue. The rate of proliferation of a stably transfected colon 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 ecdysone receptor-containing RKO cells were infected with a replication-defective recombinant 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.
Chen
X
X
Departments of Medicine and Biological Chemistry, and the Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Johns
D C
DC
Geiman
D E
DE
Marban
E
E
Dang
D T
DT
Hamlin
G
G
Sun
R
R
Yang
V W
VW
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D016466:CHO Cells; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002469:Cell Separation; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D004330:Drosophila; D004440:Ecdysone / Q000494:pharmacology; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016196:S Phase; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D004440:Ecdysone; D004441:Ecdysterone; C008999:ponasterone A; D004247:DNA