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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Title: Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development
Author: Wiedemeyer, Ruprecht; Brennan, Cameron; Heffernan, Timothy P.; Xiao, Yonghong; Mahoney, John T.; Protopopov, Alexei; Zheng, Hongwu; Bignell, Graham; Furnari, Frank; Cavenee, Webster K.; Hahn, William C.; Ichimura, Koichi; Collins, Peter V.; Chu, Gerald C.; Stratton, Michael R.; Ligon, Keith Lloyd; Futreal, Andrew P.; Chin, Lynda

Note: Order does not necessarily reflect citation order of authors.

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.
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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.
Published Version: doi:10.1016/j.ccr.2008.02.010
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292238/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4853393

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