The human secretin receptor gene: genomic organization and promoter characterization

Secretin is the most potent regulator of pancreatic bicarbonate, electrolyt e and volume secretion. In this report, the organization of the human secre tin receptor (hSR) gene was characterized by overlapping genomic phage clon es. The hSR gene consists of 13 exons and 12 introns with all the splice do nor and acceptor sites conforming to the canonical GT/AG rule, By transient reporter gene assays, the mild-type promoter, containing 3.0 kb of the hSR gene 5' flanking region, was able to drive 5.8 +/- 0.6 and 6.6 +/- 0.2-fol d (P < 0.01) increases in luciferase activities in pancreatic ductule-deriv ed PANC-1 and BPD-1 cells, respectively, By subsequent 5' and 3' deletion a nalysis, a promoter element was identified within -408 to -158, relative to the ATG codon, This promoter element was found to be cell-specific since i t could drive reporter gene expression in PANC-1 and BPD-1 cells but not in Hs 262.St, Hs 746T and alpha T3-1 cells, The study of the transcriptional control of human secretin and its receptor should shed light on the patholo gical developments of pancreatic cancer and autism in the future. (C) 1999 Federation of European Biochemical Societies.