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dc.contributor.author Wang, J
dc.contributor.author Wang, H
dc.contributor.author Li, Z
dc.contributor.author Wu, Q
dc.contributor.author Lathia, JD
dc.contributor.author McLendon, RE
dc.contributor.author Hjelmeland, AB
dc.contributor.author Rich, JN
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:26Z
dc.date.issued 2008
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/19020659
dc.identifier.citation PLoS One, 2008, 3 (11), pp. e3769 - ?
dc.identifier.uri http://hdl.handle.net/10161/4507
dc.description.abstract BACKGROUND: Malignant gliomas rank among the most lethal cancers. Gliomas display a striking cellular heterogeneity with a hierarchy of differentiation states. Recent studies support the existence of cancer stem cells in gliomas that are functionally defined by their capacity for extensive self-renewal and formation of secondary tumors that phenocopy the original tumors. As the c-Myc oncoprotein has recognized roles in normal stem cell biology, we hypothesized that c-Myc may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Based on previous methods that we and others have employed, tumor cell populations were enriched or depleted for cancer stem cells using the stem cell marker CD133 (Prominin-1). We characterized c-Myc expression in matched tumor cell populations using real time PCR, immunoblotting, immunofluorescence and flow cytometry. Here we report that c-Myc is highly expressed in glioma cancer stem cells relative to non-stem glioma cells. To interrogate the significance of c-Myc expression in glioma cancer stem cells, we targeted its expression using lentivirally transduced short hairpin RNA (shRNA). Knockdown of c-Myc in glioma cancer stem cells reduced proliferation with concomitant cell cycle arrest in the G(0)/G(1) phase and increased apoptosis. Non-stem glioma cells displayed limited dependence on c-Myc expression for survival and proliferation. Further, glioma cancer stem cells with decreased c-Myc levels failed to form neurospheres in vitro or tumors when xenotransplanted into the brains of immunocompromised mice. CONCLUSIONS/SIGNIFICANCE: These findings support a central role of c-Myc in regulating proliferation and survival of glioma cancer stem cells. Targeting core stem cell pathways may offer improved therapeutic approaches for advanced cancers.
dc.format.extent e3769 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0003769
dc.subject Animals
dc.subject Antigens, CD
dc.subject Brain Neoplasms
dc.subject Cell Cycle
dc.subject Cell Proliferation
dc.subject Gene Expression Regulation, Neoplastic
dc.subject Glioma
dc.subject Glycoproteins
dc.subject Mice
dc.subject Mice, Inbred BALB C
dc.subject Mice, Nude
dc.subject Neoplasm Transplantation
dc.subject Neoplasms
dc.subject Neoplastic Stem Cells
dc.subject Oncogene Proteins
dc.subject Peptides
dc.subject Proto-Oncogene Proteins c-myc
dc.title c-Myc is required for maintenance of glioma cancer stem cells.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2008-11-20 en_US
duke.description.endpage e3769 en_US
duke.description.issue 11 en_US
duke.description.startpage e3769 en_US
duke.description.volume 3 en_US
dc.relation.journal Plos One en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/19020659
pubs.issue 11
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published
pubs.volume 3
dc.identifier.eissn 1932-6203

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