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Am J Physiol Gastrointest Liver Physiol (July 3, 2002). doi:10.1152/ajpgi.00075.2002
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Articles in PresS, published online ahead of print July 3, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00075.2002
Submitted on February 20, 2002
Accepted on June 24, 2002

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

Toshihiro Uesaka1*, Huimei Lu1, Osamu Katoh1, and Hiromitsu Watanabe1

1 Department of Cellular Biology, Hiroshima University, Research Institute for Radiation Biology and Medicine, Hiroshima, Japan

* To whom correspondence should be addressed. E-mail: tochi{at}hiroshima-u.ac.jp.

The development and differentiation of the intestinal epithelium appear to be regulated by various growth factors. Using cDNA microarrays, we identified heparin-binding epidermal growth factor-like growth factor (HB-EGF) as one of the genes induced by an intestinal-specific transcription factor, Cdx2, in an intestinal undifferentiated rat cell line, 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. Cdx2 protein can bind to the Cdx2-binding element of the HB-EGF gene. The 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 Cdx2-fs control of the proliferation and migration of IEC-6 cells.




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