Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9823
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dc.contributor.authorPatel, Oneelen
dc.contributor.authorDumesny, Chelseaen
dc.contributor.authorGiraud, Andrew Sen
dc.contributor.authorBaldwin, Graham Sen
dc.contributor.authorShulkes, Arthuren
dc.date.accessioned2015-05-15T23:04:39Z
dc.date.available2015-05-15T23:04:39Z
dc.date.issued2004-12-01en
dc.identifier.citationBiochemical Pharmacology; 68(11): 2129-42en
dc.identifier.govdoc15498503en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/9823en
dc.description.abstractAlthough amidated forms of gastrin-releasing peptide (GRP) have been identified as autocrine growth factors in small cell lung cancer, their role in the development and progression of colorectal carcinoma is less clear. In addition, the biological activity of non-amidated gastrin-releasing peptide has not been investigated in colorectal carcinoma cells. We therefore investigated the effect of bombesin (a homologue of gastrin-releasing peptide) on proliferation, migration and inositol phosphate production in the human colorectal carcinoma cell line DLD-1, and determined the ability of gastrin-releasing peptide receptor antagonists to inhibit these effects. We also compared the biological activities of amidated and non-amidated GRP in the same assays. Treatment with either bombesin, or amidated or non-amidated GRP resulted in significant increase in proliferation, and in migration in a wound-healing assay. Both the mitogenic and migratory effects of amidated and non-amidated forms were inhibited by the GRP receptor antagonist [D-Phe(6), Leu-NHet(13), des-Met(14)]-bombesin(6-13). The presence of GRP receptor mRNA and GRP binding sites in three colorectal carcinoma cell lines was demonstrated by RT-PCR and by binding of radiolabelled bombesin, respectively. Transfection of DLD-1 cells with a dominant negative phosphatidylinositol 3-kinase did not affect bombesin-stimulated cell proliferation, but inhibited bombesin-stimulated cell migration. Bombesin and GRPgly activated phospholipase C, mitogen-activated protein kinase and focal adhesion kinase. We conclude that both amidated and non-amidated forms of gastrin-releasing peptide accelerate proliferation and migration of DLD-1 human colorectal carcinoma cells via the gastrin-releasing peptide receptor, but that phosphatidylinositol 3-kinase is only involved in the cell migration signalling pathway. Our results suggest a potential role for gastrin-releasing peptide receptor antagonists in the management of colorectal carcinoma.en
dc.language.isoenen
dc.subject.otherBombesin.pharmacologyen
dc.subject.otherCell Movement.drug effectsen
dc.subject.otherCell Proliferation.drug effectsen
dc.subject.otherColorectal Neoplasms.metabolism.pathologyen
dc.subject.otherEnzyme Activation.drug effectsen
dc.subject.otherFocal Adhesion Kinase 1en
dc.subject.otherFocal Adhesion Protein-Tyrosine Kinasesen
dc.subject.otherGastrin-Releasing Peptide.pharmacologyen
dc.subject.otherGlycine.metabolismen
dc.subject.otherHumansen
dc.subject.otherInositol Phosphates.metabolismen
dc.subject.otherMitogen-Activated Protein Kinase 1.metabolismen
dc.subject.otherPhosphatidylinositol 3-Kinases.physiologyen
dc.subject.otherProtein-Tyrosine Kinases.metabolismen
dc.subject.otherReceptors, Bombesin.analysisen
dc.subject.otherReverse Transcriptase Polymerase Chain Reactionen
dc.subject.otherTumor Cells, Cultureden
dc.titleStimulation of proliferation and migration of a colorectal cancer cell line by amidated and glycine-extended gastrin-releasing peptide via the same receptor.en
dc.typeJournal Articleen
dc.identifier.journaltitleBiochemical pharmacologyen
dc.identifier.affiliationDepartments of Surgery, Austin Hospital, University of Melbourne, Melbourne, Vic. 3084, Australiaen
dc.identifier.doi10.1016/j.bcp.2004.08.009en
dc.description.pages2129-42en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/15498503en
dc.type.austinJournal Articleen
item.fulltextNo Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
item.openairetypeJournal Article-
item.grantfulltextnone-
item.cerifentitytypePublications-
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