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dc.date.accessioned2018-06-26T09:12:31Z
dc.date.issued2002en_US
dc.identifierhttp://www.nature.com/bjc/journal/v86/n7/full/6600219a.htmlen_US
dc.identifier.citationBRITISH JOURNAL OF CANCER, 2002, 86 (7), pp. 1104 - 1109en_US
dc.identifier.issn0007-0920en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1927
dc.description.abstractDominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells. We previously reported that the FrbB2 oncoprotein prolongs and amplifies growth factor signalling by impairing ligand- dependent downregulation of hetero-oligomerised epidermal growth factor receptors. Here we show that treatment of A431 cells with different epidermal growth factor receptor ligands can cause growth inhibition to an extent paralleling ErbB2 tyrosine phosphorylation. To determine whether such growth inhibition signifies an interaction between the cell cycle machinery and b ErbB2-dependent alterations of cell signalling kinetics, we used MCF7 breast cancer cells (which express wild- type p53) to create transient and stable ErbB2 transfectants (MCF-B2). Compared with parental cells, MCF7-B2 cells are characterised by upregulation of p53, P21(WAF) and Myc, downregulation of Bcl2, and apoptosis. In contrast, MCF-B2 cells co-transfected with dominant negative p53 (MCF7- B2/Deltap53) exhibit reduced apoptosis and enhanced growth relative to both parental MCF7-B2 and control cells, These data imply that wild-type p53 limits survival of ErbB2- overexpressing breast cancer cells, and suggest b b that signals of varying length and/or intensity may evolve different cell outcomes depending upon the integrity of cell cycle control genes. We submit that acquisition of cell cycle control defects may play a permissive role in ErbB2 upregulation, and that the FrbB2 overexpression phenotype may in turn select for the survival of cells with p53 mutations or other tumour suppressor gene defects.en_US
dc.format.extent1104 - 1109en_US
dc.subjectErbB2 p53 apoptosis WILD-TYPE P53 MYC-INDUCED APOPTOSIS FACTOR RECEPTOR DOWN- REGULATION EPITHELIAL-CELLS EGF-RECEPTOR MAP KINASE A431 CELLS MUTANT P53 TYROSINE PHOSPHORYLATIONen_US
dc.titleDominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cellsen_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2002en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBRITISH JOURNAL OF CANCERen_US
pubs.issue7en_US
pubs.notespublic Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells. We previously reported that the FrbB2 oncoprotein prolongs and amplifies growth factor signalling by impairing ligand- dependent downregulation of hetero-oligomerised epidermal growth factor receptors. Here we show that treatment of A431 cells with different epidermal growth factor receptor ligands can cause growth inhibition to an extent paralleling ErbB2 tyrosine phosphorylation. To determine whether such growth inhibition signifies an interaction between the cell cycle machinery and b ErbB2-dependent alterations of cell signalling kinetics, we used MCF7 breast cancer cells (which express wild- type p53) to create transient and stable ErbB2 transfectants (MCF-B2). Compared with parental cells, MCF7-B2 cells are characterised by upregulation of p53, P21(WAF) and Myc, downregulation of Bcl2, and apoptosis. In contrast, MCF-B2 cells co-transfected with dominant negative p53 (MCF7- B2/Deltap53) exhibit reduced apoptosis and enhanced growth relative to both parental MCF7-B2 and control cells, These data imply that wild-type p53 limits survival of ErbB2- overexpressing breast cancer cells, and suggest b b that signals of varying length and/or intensity may evolve different cell outcomes depending upon the integrity of cell cycle control genes. We submit that acquisition of cell cycle control defects may play a permissive role in ErbB2 upregulation, and that the FrbB2 overexpression phenotype may in turn select for the survival of cells with p53 mutations or other tumour suppressor gene defects.en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Target Evaluation and Molecular Therapeutics
pubs.volume86en_US
pubs.embargo.termsNot knownen_US
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
icr.researchteamTarget Evaluation and Molecular Therapeuticsen_US
dc.contributor.icrauthorHobbs, Stephenen_US
dc.contributor.icrauthorWalton, Michaelen_US


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