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J. Biol. Chem., Vol. 276, Issue 10, 6897-6900, March 9, 2001
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,
, and
§¶
From the Departments of 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.
Medicine and
§ Biological Chemistry, The Johns Hopkins University School
of Medicine, Baltimore, Maryland 21205
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