Cell-specific expression of the glucose-dependent insulinotropic polypeptide gene in a mouse neuroendocrine tumor cell line.
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.
Boylan
M O
MO
Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA.
Jepeal
L I
LI
Jarboe
L A
LA
Wolfe
M M
MM
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism*; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051381:Rats; D017207:Rats, Sprague-Dawley; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D005749:Gastric Inhibitory Polypeptide