title: Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma.
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.
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, 1066CX, Amsterdam, the Netherlands.
authors.forename: Sophia W M
authors.initials: SW
authors.lastname: Bruggeman
authors.forename: Danielle
authors.initials: D
authors.lastname: Hulsman
authors.forename: Ellen
authors.initials: E
authors.lastname: Tanger
authors.forename: Tessa
authors.initials: T
authors.lastname: Buckle
authors.forename: Marleen
authors.initials: M
authors.lastname: Blom
authors.forename: John
authors.initials: J
authors.lastname: Zevenhoven
authors.forename: Olaf
authors.initials: O
authors.lastname: van Tellingen
authors.forename: Maarten
authors.initials: M
authors.lastname: van Lohuizen
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation; D009367:Neoplasm Staging; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: C069077:BMI1 protein, human; C489421:Bmi1 protein, mouse; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; C512478:EGFR protein, human; D066246:ErbB Receptors