Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development

Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development

DSpace/Manakin Repository

Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development

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