Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development
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Author
Wiedemeyer, Ruprecht
Brennan, Cameron
Xiao, Yonghong
Zheng, Hongwu
Bignell, Graham
Furnari, Frank
Cavenee, Webster K.
Ichimura, Koichi
Collins, Peter V.
Stratton, Michael R.
Futreal, Andrew P.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1016/j.ccr.2008.02.010Metadata
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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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292238/pdf/Terms of Use
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