title: Bombesin enhances TGF-beta growth inhibitory effect through apoptosis induction in intestinal epithelial cells.
abstract: Mammalian intestinal epithelium undergoes continuous cell turn over, with cell proliferation in the crypts and apoptosis in the villus. Both transforming growth factor (TGF)-beta and gastrin-releasing peptide (GRP) are involved in the regulation of intestinal epithelial cells for division, differentiation, adhesion, migration and death. Previously, we have shown that TGF-beta and bombesin (BBS) synergistically induce cyclooxygenase-2 (COX-2) expression and subsequent prostaglandin E(2) (PGE2) production through p38(MAPK) in rat intestinal epithelial cell line stably transfected with GRP receptor (RIE/GRPR), suggesting the interaction between TGF-beta signaling pathway and GRPR. The current study examined the biological responses of RIE/GRPR cells to TGF-beta and BBS. Treatment with TGF-beta1 (40 pM) and BBS (100 nM) together synergistically inhibited RIE/GRPR growth and induced apoptosis. Pretreatment with SB203580 (10 microM), a specific inhibitor of p38(MAPK), partially blocked the synergistic effect of TGF-beta and BBS on apoptosis. In conclusion, BBS enhanced TGF-beta growth inhibitory effect through apoptosis induction, which is at least partially mediated by p38(MAPK).
authors.affiliation: Department of Surgery, University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Liu
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhao
authors.forename: Fazhi
authors.initials: F
authors.lastname: Li
authors.forename: Yan-shi
authors.initials: YS
authors.lastname: Guo
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellmich
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Townsend
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cao
authors.forename: Tien C
authors.initials: TC
authors.lastname: Ko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001839:Bombesin / Q000494:pharmacology*; D002453:Cell Cycle; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases; D001839:Bombesin