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All‐ trans retinoic acid inhibits proliferation of intestinal epithelial cells by inhibiting expression of the gene encoding Krüppel‐like factor 5
Author(s) -
Chanchevalap Sengthong,
Nandan Mandayam O.,
Merlin Didier,
Yang Vincent W.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.079
Subject(s) - retinoic acid , cell growth , transfection , retinoid , microbiology and biotechnology , cell culture , transcription factor , biology , growth inhibition , 3t3 cells , tretinoin , cell cycle , chemistry , cell , cancer research , gene , biochemistry , genetics
Retinoids are known inhibitors of epithelial cell proliferation. Previous studies indicate that Krüppel‐like factor 5 (KLF5) is a pro‐proliferative transcription factor. Here, we examined the effect of all‐ trans retinoid acid (ATRA) on proliferation of the intestinal epithelial cell line, IEC6. Treatment of IEC6 cells with ATRA inhibited their proliferation due to G 1 cell cycle arrest. This inhibition was correlated with a decrease in the levels of KLF5 mRNA and promoter activity. In contrast, constitutive expression of KLF5 in stably transfected IEC6 cells with a KLF5‐expressing plasmid driven by a viral promoter abrogated the growth inhibitory effect of ATRA. Moreover, ATRA inhibited proliferation of several human colon cancer cell lines with high levels of KLF5 expression but not those with low levels of KLF5 expression. Our results indicate that KLF5 is a potential mediator for the inhibitory effect of ATRA on intestinal epithelial cell proliferation.