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Am J Physiol Gastrointest Liver Physiol 283: G840-G847, 2002. First published July 3, 2002; doi:10.1152/ajpgi.00075.2002
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Vol. 283, Issue 4, G840-G847, October 2002

Heparin-binding EGF-like growth factor gene transcription regulated by Cdx2 in the intestinal epithelium

Toshihiro Uesaka, Huimei Lu, Osamu Katoh, and Hiromitsu Watanabe

Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan

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 epithetial 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.

enterocyte; intestinal epithelial cell-6


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