The caudal homeobox protein cdx-2/3 activates endogenous proglucagon gene expression in InR1-G9 islet cells

被引:39
作者
Jin, TR [1 ]
Trinh, DKY [1 ]
Wang, F [1 ]
Drucker, DJ [1 ]
机构
[1] UNIV TORONTO, TORONTO HOSP, DEPT MED, BANTING & BEST DIABET CTR, TORONTO, ON M5G 2C4, CANADA
关键词
D O I
10.1210/me.11.2.203
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The proglucagon gene is expressed in a highly cell-specific manner in islet and enteroendocrine cells. DNA sequences within the proximal proglucagon G1 promoter region bind the homeobox protein cdx-2/3, and cdx-2/3 activates the proglucagon promoter in fibroblasts. We show here that cdx-2/3 activates the proglucagon promoter in both islet (InR1-G9) and enteroendocrine (STC-1 and GLUTag) cell lines, Furthermore, transfected cdx-2/3 increased the levels of endogenous proglucagon mRNA transcripts in both transient and stable transfections of InR1-G9 islet cells. The cdx-2/3-dependent induction of endogenous proglucagon mRNA transcripts in stable islet lines was associated with a corresponding increase in the transcriptional activity of proglucagon promoter-luciferase plasmids, An amino-terminally truncated cdx-2/3 derivative containing the homeodomain and carboxy-terminal region of the molecule inhibited both the cdx-2/3 activation of the proglucagon promoter and the induction of endogenous proglucagon mRNA transcripts, These observations demonstrate that cdx-2/3, acting through the proximal G1 element, is a major transcriptional determinant of cell-specific proglucagon gene expression in pancreatic islet cells.
引用
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页码:203 / 209
页数:7
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