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dc.contributor.authorHe, Hongen
dc.contributor.authorYim, Mildreden
dc.contributor.authorLiu, Kevin Hen
dc.contributor.authorCody, Stephen Cen
dc.contributor.authorShulkes, Arthuren
dc.contributor.authorBaldwin, Graham Sen
dc.identifier.citationCellular Signalling 2007; 20(1): 83-93en
dc.description.abstractGastrins, including amidated gastrin (Gamide) and glycine-extended gastrin (Ggly), are known to accelerate the growth of gastric and colorectal cancer cells by stimulation of proliferation and inhibition of apoptosis. Gamide controls apoptosis by regulation of proteins of the Bcl-2 family and by regulation of the activation of caspases. However the interactions between Ggly and proteins of the Bcl-2 family and caspases are not known. Since in other systems G proteins of the Rho family inhibit apoptosis via interaction with proteins of the Bcl-2 family, leading to changes in caspase activities, we have compared the role of Rho family G proteins in regulation of Bcl-2-like (Bad/Bax/Bcl-xl) protein expression and caspase 3 activation by Ggly and Gamide. The effects of the specific inhibitors C3 (for Rho) and Y-27632 (for ROCK), and of dominant negative mutants of Rac, Cdc42 and PAK, were investigated in the gastric epithelial cell line IMGE-5. Apoptosis was induced by serum starvation and confirmed by annexin V staining and caspase 3 activation. Ggly inhibits caspase 3 activation via a Bcl-2-like protein-mediated pathway which requires activation of both Rho/ROCK and Rac/Cdc42/PAK. Gamide inhibits caspase 3 activation via redundant Bcl-2-like protein-mediated pathways which involve alternative activation of Rac/Cdc42/PAK and Rho/ROCK. Gamide and Ggly differentially activate members of Rho family G proteins which in turn regulate different proteins of the Bcl-2 family leading to changes in caspase 3 activity. The findings offer potential targets for blocking the growth-stimulating effects of these gastrins.en
dc.subject.otherApoptosis.drug effectsen
dc.subject.otherCaspase 3.metabolismen
dc.subject.otherCell Lineen
dc.subject.otherEnzyme Inhibitors.pharmacologyen
dc.subject.otherEpithelial Cells.metabolismen
dc.subject.otherGastric Mucosa.cytology.metabolismen
dc.subject.otherMice, Transgenicen
dc.subject.otherProto-Oncogene Proteins c-akt.metabolismen
dc.subject.otherProto-Oncogene Proteins c-bcl-2.metabolismen
dc.subject.otherSignal Transduction.physiologyen
dc.subject.otherbcl-2-Associated X Protein.metabolismen
dc.subject.otherbcl-X Protein.metabolismen
dc.subject.othercdc42 GTP-Binding Protein.metabolismen
dc.subject.otherp21-Activated Kinases.metabolismen
dc.subject.otherrho GTP-Binding Proteins.metabolismen
dc.subject.otherrho-Associated Kinases.metabolismen
dc.titleInvolvement of G proteins of the Rho family in the regulation of Bcl-2-like protein expression and caspase 3 activation by Gastrins.en
dc.typeJournal Articleen
dc.identifier.journaltitleCellular signallingen
dc.identifier.affiliationDepartment of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia 3084, Australiaen
dc.type.austinJournal Articleen, Hong
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en- (University of Melbourne)-
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