MUC1-C Oncoprotein Blocks Terminal Differentiation of Chronic Myelogenous Leukemia Cells by a ROS-Mediated Mechanism.

ABSTRACT: Chronic myelogenous leukemia (CML) inevitably progresses to a blast phase by mechanisms that are not well understood. The MUC1-C oncoprotein is expressed in CML blasts but not chronic phase cells. The present studies demonstrate that treatment of KU812 and K562 CML cells with a cell-penetrating MUC1-C inhibitor, designated GO-203, is associated with increases in reactive oxygen species (ROS) and depletion of glutathione. GO-203 treatment resulted in the complete downregulation of Bcr-Abl expression and induced cell cycle arrest by a ROS-mediated mechanism that was blocked by the antioxidant N-acetylcysteine. Progression of CML to blast crisis has been linked to dysregulation of Wnt/β-catenin signaling and an arrest of differentiation. The present results show that inhibition of MUC1-C indu

SUBMITTER: Yin L 

PROVIDER: S-EPMC3107545 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature