Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/13643
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dc.contributor.authorJohnstone, R Wen
dc.contributor.authorCretney, Een
dc.contributor.authorSmyth, Mark Jen
dc.date.accessioned2015-05-16T03:31:19Z
dc.date.available2015-05-16T03:31:19Z
dc.date.issued1999-02-01en
dc.identifier.citationBlood; 93(3): 1075-85en
dc.identifier.govdoc9920858en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/13643en
dc.description.abstractA major problem with treating patients with cancer by traditional chemotherapeutic regimes is that their tumors often develop a multidrug resistant (MDR) phenotype and subsequently become insensitive to a range of different chemotoxic drugs. One cause of MDR is overexpression of the drug-effluxing protein, P-glycoprotein. It is now apparent that P-glycoprotein may also possess a more generic antiapoptotic function that protects P-glycoprotein-expressing cancer cells and normal cells from cell death. Herein we show that cells induced to express P-glycoprotein either by drug selection or by retroviral gene transduction with MDR1 cDNA are resistant to cell death induced by a wide range of death stimuli, such as FasL, tumor necrosis factor (TNF), and ultraviolet (UV) irradiation, that activate the caspase apoptotic cascade.However, P-glycoprotein-expressing cells were not resistant to caspase-independent cell death mediated by pore-forming proteins and granzyme B.MDR P-glycoprotein-expressing cells were made sensitive to caspase-dependent apoptosis by the addition of anti-P-glycoprotein antibodies or verapamil, a pharmacological inhibitor of P-glycoprotein function. Clonogenic assays showed that P-glycoprotein confers long-term resistance to caspase-dependent apoptotic stimuli but not to caspase-independent cell death stimuli. This study has confirmed a potential novel physiological function for P-glycoprotein and it now remains to dissect the molecular mechanisms involved in the inhibition of capsase-dependent cell death by P-glycoprotein.en
dc.language.isoenen
dc.subject.otherAntibodies, Monoclonal.pharmacologyen
dc.subject.otherAntigens, CD95.physiologyen
dc.subject.otherAntineoplastic Agents.pharmacologyen
dc.subject.otherApoptosis.drug effects.physiology.radiation effectsen
dc.subject.otherCaspases.physiologyen
dc.subject.otherCytotoxicity, Immunologicen
dc.subject.otherDNA, Complementary.geneticsen
dc.subject.otherDexamethasone.pharmacologyen
dc.subject.otherEnzyme Inhibitors.pharmacologyen
dc.subject.otherEtoposide.pharmacologyen
dc.subject.otherFas Ligand Proteinen
dc.subject.otherGenes, MDRen
dc.subject.otherGranzymesen
dc.subject.otherHumansen
dc.subject.otherLeukemia-Lymphoma, Adult T-Cell.pathologyen
dc.subject.otherMembrane Glycoproteins.pharmacologyen
dc.subject.otherNeoplasm Proteins.physiologyen
dc.subject.otherP-Glycoprotein.genetics.physiologyen
dc.subject.otherPerforinen
dc.subject.otherPore Forming Cytotoxic Proteinsen
dc.subject.otherRecombinant Proteins.pharmacologyen
dc.subject.otherSerine Endopeptidases.pharmacologyen
dc.subject.otherTransfectionen
dc.subject.otherTumor Necrosis Factor-alpha.pharmacologyen
dc.subject.otherTumor Stem Cell Assayen
dc.subject.otherUltraviolet Raysen
dc.subject.otherVerapamil.pharmacologyen
dc.subject.otherVinblastine.pharmacologyen
dc.titleP-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death.en
dc.typeJournal Articleen
dc.identifier.journaltitleBlooden
dc.identifier.affiliationThe Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.description.pages1075-85en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/9920858en
dc.type.austinJournal Articleen
item.grantfulltextnone-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
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