Problem: The expression of the human cholecystokinin-B/gastrin receptor has been reported in human colorectal cancers. Recently, a novel gastrin receptor has been cloned. The purpose of the present study was to determine whether the novel
gastrin receptor transactiviates COX-2 promoter in human colon cancer cells and in COS-7 cells.
Methods: Both cells were transfected with wild type and novel gastrin captors. Stimulated with gastrin-17, transactivation of COX-2 promoter was determined by luciferase reporter gene assay. Induction of COX-2 expression was explored at the mRNA
and protein level using real time RT-PCR and Western blotting. Prostaglandin E2 secretion was measured by ELISA.
Results: Gastrin transactivates the COX-2 promoter in both cells. Three pathways are required for the transactivation of COX-2. Gastrin increased mRNA expression and stimulated PGE2 secretion.
Discussion: The novel gastrin receptor transactiviates COX-2 and is thus likely to confer oncogenic properties.