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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 AC133 Antigen
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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