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dc.contributor.authorLim, Yi Chieh
dc.contributor.authorRoberts, Tara
dc.contributor.authorDay, Bryan
dc.contributor.authorHarding, Angus
dc.contributor.authorKozlov, Sergei
dc.contributor.authorKijas, Amanda
dc.contributor.authorEnsbey, Kathleen
dc.contributor.authorWalker, David
dc.contributor.authorLavin, Martin
dc.date.accessioned2017-05-03T14:21:04Z
dc.date.available2017-05-03T14:21:04Z
dc.date.issued2012
dc.date.modified2013-09-17T23:35:06Z
dc.identifier.issn1535-7163
dc.identifier.doi10.1158/1535-7163.MCT-11-1044
dc.identifier.urihttp://hdl.handle.net/10072/53208
dc.description.abstractGlioblastoma multiforme (GBM) is the most common form of brain tumor with a poor prognosis and resistance to radiotherapy. Recent evidence suggests that glioma-initiating cells play a central role in radioresistance through DNA damage checkpoint activation and enhanced DNA repair. To investigate this in more detail, we compared the DNA damage response in nontumor forming neural progenitor cells (NPC) and glioma-initiating cells isolated from GBM patient specimens. As observed for GBM tumors, initial characterization showed that glioma-initiating cells have long-term self-renewal capacity. They express markers identical to NPCs and have the ability to form tumors in an animal model. In addition, these cells are radioresistant to varying degrees, which could not be explained by enhanced nonhomologous end joining (NHEJ). Indeed, NHEJ in glioma-initiating cells was equivalent, or in some cases reduced, as compared with NPCs. However, there was evidence for more efficient homologous recombination repair in glioma-initiating cells. We did not observe a prolonged cell cycle nor enhanced basal activation of checkpoint proteins as reported previously. Rather, cell-cycle defects in the G1-S and S-phase checkpoints were observed by determining entry into S-phase and radioresistant DNA synthesis following irradiation. These data suggest that homologous recombination and cell-cycle checkpoint abnormalities may contribute to the radioresistance of glioma-initiating cells and that both processes may be suitable targets for therapy.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1863
dc.relation.ispartofpageto1872
dc.relation.ispartofissue9
dc.relation.ispartofjournalMolecular Cancer Therapeutics
dc.relation.ispartofvolume11
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode3214
dc.titleA role for homologous recombination and abnormal cell-cycle progression in radioresistance of glioma-initiating cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorWalker, David G.


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