Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development

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Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development

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dc.contributor.author Wiedemeyer, Ruprecht
dc.contributor.author Brennan, Cameron
dc.contributor.author Heffernan, Timothy P.
dc.contributor.author Xiao, Yonghong
dc.contributor.author Mahoney, John T.
dc.contributor.author Protopopov, Alexei
dc.contributor.author Zheng, Hongwu
dc.contributor.author Bignell, Graham
dc.contributor.author Furnari, Frank
dc.contributor.author Cavenee, Webster K.
dc.contributor.author Hahn, William C.
dc.contributor.author Ichimura, Koichi
dc.contributor.author Collins, Peter V.
dc.contributor.author Chu, Gerald C.
dc.contributor.author Stratton, Michael R.
dc.contributor.author Ligon, Keith Lloyd
dc.contributor.author Futreal, Andrew P.
dc.contributor.author Chin, Lynda
dc.date.accessioned 2011-04-18T00:07:33Z
dc.date.issued 2008
dc.identifier.citation Wiedemeyer, Ruprecht, Cameron Brennan, Timothy P. Heffernan, Yonghong Xiao, John Mahoney, Alexei Protopopov, Hongwu Zheng, et al. 2008. Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development. Cancer Cell 13(4): 355-364. en_US
dc.identifier.issn 1535-6108 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4853393
dc.description.abstract We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18^{INK4C} and p16^{INK4A} codeletion. Functional reconstitution of p18^{INK4C} in GBM cells null for both p16^{INK4A} and p18^{INK4C} resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16^{INK4A}-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16^{INK4A} in primary astrocytes induced a concomitant increase in p18^{INK4C}. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18^{INK4C} in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation. en_US
dc.language.iso en_US en_US
dc.publisher Cell Press en_US
dc.relation.isversionof doi:10.1016/j.ccr.2008.02.010 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292238/pdf/ en_US
dash.license LAA
dc.subject cell cycle en_US
dc.title Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development en_US
dc.type Journal Article en_US
dc.description.version Accepted Manuscript en_US
dc.relation.journal Cancer Cell en_US
dash.depositing.author Chin, Lynda
dc.date.available 2011-04-18T00:07:33Z
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Dermatology-Brigham and Women's Hospital en_US

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