Involvement of cyclooxygenase-2 in proliferation and morphogenesis inducedby transforming growth factor alpha in gastric epithelial cells

Transforming growth factor or is one of the most potent growth factors for gastrointestinal epithelium. In this study, we examined the roles of cycloo xygenase-2 on proliferation and morphogenesis of RGM1 rat gastric epithelia l cells after stimulation with transforming growth factor alpha in vitro, R GM1 cells increased expression of cyclooxygenase-2 messenger RNA 20-60 min after stimulation with transforming growth factor alpha. Transforming growt h factor a stimulated [H-3]thymidine incorporation and tubulogenesis of RGM 1 cells in collagen matrix, both of which were significantly suppressed by treatment with a cyclooxygenase-2 specific inhibitor, NS-398 or cyclooxygen ase-2 antisense oligonucleotide. Both of the treatment lowered prostanoid p roduction by enzyme immunoassay. The transforming growth factor alpha-induc ed expression of cyclooxygenase-2 is followed by cell proliferation and dev elopment of tubular morphology of RGM1 gastric epithelial cells. Treatment with cyclooxygenase-2 inhibitor and cyclooxygenase-2 antisense oligonucleot ide suppressed these responses induced by transforming growth factor a sugg esting the involvement of cyclooxygenase-2 in proliferation and morphogenes is in gastric mucosal epithelium. (C) 1999 Harcourt Publishers Ltd.