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      Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma.

      Cancer Cell
      3T3 Cells, Animals, Astrocytes, metabolism, pathology, Brain Neoplasms, genetics, Cell Differentiation, Cell Proliferation, Cell Transformation, Neoplastic, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p16, deficiency, Gene Expression Regulation, Neoplastic, Glioblastoma, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Nude, Mutation, Neoplasm Staging, Neoplasms, Experimental, Neurons, Nuclear Proteins, Phenotype, Polycomb Repressive Complex 1, Proto-Oncogene Proteins, Receptor, Epidermal Growth Factor, Repressor Proteins, Signal Transduction, Stem Cells, Time Factors, Transduction, Genetic

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          Abstract

          The Polycomb group and oncogene Bmi1 is required for the proliferation of various differentiated cells and for the self-renewal of stem cells and leukemic cancer stem cells. Repression of the Ink4a/Arf locus is a well described mechanism through which Bmi1 can exert its proliferative effects. However, we now demonstrate in an orthotopic transplantation model for glioma, a type of cancer harboring cancer stem cells, that Bmi1 is also required for tumor development in an Ink4a/Arf-independent manner. Tumors derived from Bmi1;Ink4a/Arf doubly deficient astrocytes or neural stem cells have a later time of onset and different histological grading. Moreover, in the absence of Ink4a/Arf, Bmi1-deficient cells and tumors display changes in differentiation capacity.

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