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(Received for publication, August 12, 1997)
From the The development of the pancreas appears to be
regulated by various growth factors. We report here the expression of
heparin-binding epidermal growth factor (EGF)-like growth factor
(HB-EGF) in the developing pancreas. Immunostaining of fetal and
neonatal rat pancreata, in which endocrine cells are visible as cell
clusters often associated with primitive ducts or ductular cells,
revealed that most of the cluster-forming cells and primitive ducts or ductular cells express HB-EGF protein. In contrast, the exocrine pancreas lacked HB-EGF expression. Based on findings that the expression pattern was similar to that of the homeodomain-containing transcription factor PDX-1 (IDX-1/STF-1/IPF1) and that the regulatory region of the HB-EGF gene contained sequences similar to the
PDX-1-binding A element, we examined whether PDX-1 could be a potential
activator of HB-EGF gene expression. The results of reporter gene
analyses suggested that the HB-EGF gene promoter is PDX-1-responsive
and that the activity of the promoter in pancreatic beta cell-derived
Volume 272, Number 46,
Issue of November 14, 1997
pp. 29137-29143
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Expression of Heparin-binding Epidermal Growth Factor-like Growth
Factor during Pancreas Development
A POTENTIAL ROLE OF PDX-1 IN TRANSCRIPTIONAL ACTIVATION
§
,
,
,
,
,
First and ¶ Second Department of
Medicine and § Department of Biochemistry, Osaka University
School of Medicine, Suita 565, Japan
TC1 cells depends on the PDX-1 binding site-like sequences.
Gel-mobility shift analyses using an anti-PDX-1 antibody indicated that
PDX-1 is a specific and dominant binding factor for an A element-like sequence in the HB-EGF gene. These observations suggest the possible involvement of HB-EGF in pancreas development. While PDX-1 is essential
for pancreas development, HB-EGF may function as a mediator of PDX-1
and thus be involved in the development of the endocrine pancreas.
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