Intestinal-enriched Krüppel-like factor (Krüppel-like factor 5) is a positive regulator of cellular proliferation.
Intestinal-enriched Krüppel-like factor (IKLF or KLF5) belongs to the family of mammalian Krüppel-like transcription factors. Previous studies indicate that expression of IKLF is enriched in the proliferating crypt epithelial cells of the intestinal tract. However, the biological function of IKLF is unknown. In the current study, we have shown that the level of IKLF mRNA was nearly undetectable in serum-deprived NIH3T3 fibroblasts but became acutely and significantly increased upon the addition of fetal bovine serum or the phorbol ester, PMA. This induction required protein synthesis because it was prevented by cycloheximide. Transfection of IKLF into NIH3T3 cells resulted in the formation of foci in a manner similar to that caused by the activated Ha-ras oncogene. Constitutive expression of IKLF in transfected NIH3T3 cells significantly increased the rate of proliferation when compared with cells transfected with an empty vector. The growth of IKLF-transfected cells was no longer inhibited by cell-cell contact or by low serum content. Moreover, these cells proliferated in an anchorage-independent fashion. We conclude that IKLF encodes a delayed early response gene product that positively regulates cellular proliferation and may give rise to a transformed phenotype when overexpressed.
Sun
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Departments of Medicine and Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Chen
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Yang
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D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002417:Cattle; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D007413:Intestinal Mucosa / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection
D016895:Culture Media, Serum-Free; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D003513:Cycloheximide; D016283:Proto-Oncogene Proteins p21(ras); D013755:Tetradecanoylphorbol Acetate