Intestinal-enriched Kruppel-like factor (Kruppel-like factor 5) is a positive regulator of cellular proliferation

Intestinal-enriched Kruppel-like factor (IKLF or KLF5) belongs to the famil y of mammalian Kruppel-like transcription factors. Previous studies indicat e 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 w as nearly undetectable in serum-deprived NIH3T3 fibroblasts but became acut ely and significantly increased upon the addition of fetal bovine serum or the phorbol ester, PMA. This induction required protein synthesis because i t was prevented by cycloheximide. Transfection of IKLF into NIH3T3 cells re sulted in the formation of foci in a manner similar to that caused by the a ctivated Ha-ras oncogene. Constitutive expression of IKLF in transfected NI H3T3 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. W e conclude that IKLF encodes a delayed early response gene product that pos itively regulates cellular proliferation and may give rise to a transformed phenotype when overexpressed.