title: Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth.
abstract: Fizzy-related (fzr) is a recently identified 7WD domain family member implicated in cell cycle regulation of Drosophila and yeast. In this study, the murine homologue of fzr was isolated by suppression subtractive hybridization as a gene with decreased expression during malignant progression of a murine B-lymphoma cell line. Retroviral overexpression of fzr in B-lymphoma cells reduced tumor formation. Those tumors that did arise had diminished or extinguished retroviral Fzr. Surprisingly, fzr overexpression dramatically increased B-lymphoma cell susceptibility to natural killer cell (NK) cytotoxicity, a host-resistant mechanism for tumor formation in this model system. These findings implicate fzr as a new category of genes suppressing B-cell tumorigenesis and suggest a novel role for fzr in the target cell interaction with NK cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095-1732, USA.
authors.forename: C X
authors.initials: CX
authors.lastname: Wang
authors.forename: B C
authors.initials: BC
authors.lastname: Fisk
authors.forename: M
authors.initials: M
authors.lastname: Wadehra
authors.forename: H
authors.initials: H
authors.lastname: Su
authors.forename: J
authors.initials: J
authors.lastname: Braun
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004330:Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C577585:Fzr1 protein, mouse; D019476:Insect Proteins; C577674:fzr protein, Drosophila