RT Journal Article
SR Electronic
T1 Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 525
OP 529
DO 10.1136/gut.50.4.525
VO 50
IS 4
A1 C Domon-Dell
A1 Q Wang
A1 S Kim
A1 M Kedinger
A1 B M Evers
A1 J-N Freund
YR 2002
UL http://gut.bmj.com/content/50/4/525.abstract
AB Background: The transcription factor encoded by the intestinal Cdx2 homeobox gene and treatment with sodium butyrate (NaB), a byproduct of fibre fermentation by colonic bacteria, exert similar effects on colon cancer cell lines as they both inhibit cell growth and stimulate cell differentiation and apoptosis. Aim: To investigate whether NaB regulates expression of the Cdx2 gene in colon cancer cell lines. Methods: Human adenocarcinoma cell lines Caco2 and HT29 were grown in the presence or absence of NaB. Cells were analysed for Cdx2 mRNA expression by reverse transcription-polymerase chain reaction, for protein expression by western blotting and electromobility shift assays, and for transcriptional activity of the Cdx2 promoter by transfection with luciferase reporter plasmids. Results: In HT29 and Caco2 cells, NaB stimulated Cdx2 mRNA and protein expression as well as transcriptional activity of the Cdx2 promoter. Stimulation of the activity of the Cdx2 promoter by NaB was dose and time dependent. The Cdx2 promoter contains discrete regions that participate in or inversely that blunt the stimulatory effect exerted by NaB. In addition, NaB stimulated the transcriptional activity of the Cdx2 promoter downregulated by oncogenic ras. Conclusion: This study is the first report of an intestine specific transcription factor, Cdx2, stimulated by butyrate. Thus it provides a new mechanism whereby butyrate controls proliferation and differentiation of colon cancer cells.