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Volume 272, Number 28, Issue of July 11, 1997 pp. 17438-17443
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Cell-specific Expression of the Glucose-dependent Insulinotropic Polypeptide Gene in a Mouse Neuroendocrine Tumor Cell Line

(Received for publication, February 19, 1997)

Michael O. Boylan , Lisa I. Jepeal , Linda A. Jarboe and M. Michael Wolfe

From the Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118

Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid gastrointestinal regulatory peptide that, in the presence of glucose, stimulates insulin secretion. GIP is expressed in K cells of the small intestine and in cells of the submandibular salivary gland. Using a rat GIP cDNA as a specific probe, we screened a number of established cell lines for the expression of GIP mRNA. STC-1 cells, a cell line derived from a mouse neuroendocrine tumor, were found to express high levels of GIP mRNA. GIP-specific transcripts were not detected in other cell lines tested, which included cells of intestinal, salivary, and endocrine origin. Analysis of GIP-luciferase fusions identified two promoters, a distal and a proximal promoter, upstream of the translation initiation codon for GIP. The distal promoter, located upstream of position +1, corresponds to the principal promoter of the GIP gene and can promote cell-specific transcription. Sequential deletion and site-directed mutational analysis of the distal promoter demonstrated that the sequence between -193 and -182 determines cell-specific expression of GIP. Contained in this region is a consensus GATA motif, suggesting that a member of the GATA family of DNA-binding proteins is involved in the cell-specific regulation of the GIP gene.


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