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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Astrocytes / metabolism*
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Astrocytes / pathology
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism*
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Brain Neoplasms / pathology
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Cell Differentiation
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Cell Proliferation
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p16 / deficiency
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Gene Expression Regulation, Neoplastic
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Glioblastoma / genetics
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Glioblastoma / metabolism*
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Glioblastoma / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Nude
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Mutation
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Neoplasm Staging
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Neurons / metabolism*
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Neurons / pathology
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phenotype
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Polycomb Repressive Complex 1
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction* / genetics
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Stem Cells / metabolism*
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Stem Cells / pathology
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Time Factors
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Transduction, Genetic
Substances
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BMI1 protein, human
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Bmi1 protein, mouse
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Cdkn2a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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Nuclear Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Polycomb Repressive Complex 1
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EGFR protein, human
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ErbB Receptors