Author/Authors :
Wiedemeyer، نويسنده , , Ruprecht and Brennan، نويسنده , , Cameron and Heffernan، نويسنده , , Timothy P. and Xiao، نويسنده , , Yonghong and Mahoney، نويسنده , , John and Protopopov، نويسنده , , Alexei and Zheng، نويسنده , , Hongwu and Bignell، نويسنده , , Graham and Furnari، نويسنده , , Frank and Cavenee، نويسنده , , Webster K. and Hahn، نويسنده , , William C. and Ichimura، نويسنده , , Koichi and Collins، نويسنده , , V. Peter and Chu، نويسنده , , Gerald C. and Stratton، نويسنده , , Michael R. and Ligon، نويسنده , , Keith L. and Futreal، نويسنده , , P. Andrew and Chin، نويسنده , , Lynda، نويسنده ,
Abstract :
Summary
e developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
