All-trans retinoic acid inhibits proliferation of intestinal epithelial cells by inhibiting expression of the gene encoding Kruppel-like factor 5.
Retinoids are known inhibitors of epithelial cell proliferation. Previous studies indicate that Kruppel-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 G1 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.
Chanchevalap
Sengthong
S
Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, 201 Whitehead Research Building, 615 Michael Street, Atlanta, GA, USA.
Nandan
Mandayam O
MO
Merlin
Didier
D
Yang
Vincent W
VW
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D015534:Trans-Activators; D014212:Tretinoin