Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/13643
Full metadata record
DC FieldValueLanguage
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.urihttps://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.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

18
checked on Mar 28, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.