Heparin-binding EGF-like growth factor gene transcription regulated by Cdx2 in the intestinal epithelium.
Development and differentiation of the intestinal epithelium appear to be regulated by various growth factors. Using cDNA microarrays, we identified heparin-binding EGF-like growth factor (HB-EGF) as one of the genes induced by intestinal-specific transcription factor Cdx2 in an intestinal undifferentiated rat cell line, intestinal epithelial cell (IEC)-6. Both Cdx2 and HB-EGF stimulated cell proliferation and migration, and their effects were inhibited partially by an EGF receptor-specific tyrosine kinase inhibitor, PD-153035. HB-EGF may function as one of the mediators of Cdx2 and may be associated with the proliferation and migration in the intestinal epithelium. The Cdx2 protein can bind to the Cdx2-binding element of the HB-EGF gene. Reporter gene analyses showed that the HB-EGF gene promoter is Cdx2 responsive and that the activity of the promoter in the IEC-6 cells depends on the number of consensus Cdx2-binding site-like sequences. These data indicate that HB-EGF gene expression can be regulated by Cdx2 and serves to mediate the control of Cdx2 of the proliferation and migration of IEC-6 cells.
Uesaka
Toshihiro
T
Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan. tochi@hiroshima-u.ac.jp
Lu
Huimei
H
Katoh
Osamu
O
Watanabe
Hiromitsu
H
D000818:Animals; D000071616:CDX2 Transcription Factor; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D018398:Homeodomain Proteins / Q000235:genetics / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000071616:CDX2 Transcription Factor; D004791:Enzyme Inhibitors; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011799:Quinazolines; D015534:Trans-Activators; D004815:Epidermal Growth Factor; D006493:Heparin; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline