title: A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition.
abstract: Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor.
authors.affiliation: Instituto de Biologia Molecular e Celular, Universidade do Porto, 4099 Porto, Portugal. sara.silva@ibmc.up.pt
authors.forename: Sara
authors.initials: S
authors.lastname: Morais da Silva
authors.forename: Tatiana
authors.initials: T
authors.lastname: Moutinho-Santos
authors.forename: Claudio E
authors.initials: CE
authors.lastname: Sunkel
mesh_terms: D000782:Aneuploidy; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster; D055785:Gene Knockdown Techniques; D060227:Imaginal Discs / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D064246:Mad2 Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C500975:Bub3 protein, Drosophila; C506005:BubR1 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D064246:Mad2 Proteins; D025521:Tumor Suppressor Proteins